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1. Safety of Plasma Infusions in Parkinson's Disease

Author

Raumin S. Neuville, Kristopher Kapphahn, Varsha Prabhakar, Maria L. Coburn, Gayle K. Deutsch, Chioma Anidi, Jordan E. Parker, Helen Bronte-Stewart, Neil P. Shah, Melanie Lising, and Amaris Martinez

Subjects
Male, 0301 basic medicine, Aging, Movement disorders, Parkinson's disease, Deep Brain Stimulation, Disease, Neuropsychological Tests, Severity of Illness Index, Antiparkinson Agents, Plasma, 0302 clinical medicine, young plasma, Research Articles, Aged, 80 and over, Parkinson Disease, Middle Aged, Combined Modality Therapy, Biomechanical Phenomena, Neurology, Tolerability, Female, Fresh frozen plasma, medicine.symptom, Research Article, Risk, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Blood Component Transfusion, Speech Disorders, 03 medical and health sciences, Rating scale, Internal medicine, medicine, Humans, Adverse effect, Aged, Interleukin-6, Tumor Necrosis Factor-alpha, business.industry, COVID-19, medicine.disease, infusions, 030104 developmental biology, Feasibility Studies, Neurology (clinical), Cognition Disorders, business, 030217 neurology & neurosurgery
Abstract

Background Young plasma infusions have emerged as a potential treatment for neurodegenerative disease, and convalescent plasma therapy has been used safely in the management of viral pandemics. However, the effect of plasma therapy in Parkinson's disease (PD) is unknown. Objectives The objective of this study was to determine the safety, tolerability, and feasibility of plasma infusions in people with PD. Methods A total of 15 people with clinically established PD, at least 1 cognitive complaint, and on stable therapy received 1 unit of young fresh frozen plasma twice a week for 4 weeks. Assessments and adverse effects were performed/reported on and off therapy at baseline, immediately after, and 4 weeks after the infusions ended. Adverse effects were also assessed during infusions. The primary outcomes were safety, tolerability, and feasibility. Exploratory outcomes included Unified Parkinson's Disease Rating Scale Part III off medication, neuropsychological battery, Parkinson's Disease Questionnaire‐39, inflammatory markers (tumor necrosis factor‐α, interleukin‐6), uric acid, and quantitative kinematics. Results Adherence rate was 100% with no serious adverse effects. There was evidence of improvement in phonemic fluency (P = 0.002) and in the Parkinson's Disease Questionnaire‐39 stigma subscore (P = 0.013) that were maintained at the delayed evaluation. Elevated baseline tumor necrosis factor‐α levels decreased 4 weeks after the infusions ended. Conclusions Young fresh frozen plasma was safe, feasible, and well tolerated in people with PD, without serious adverse effects and with preliminary evidence for improvements in phonemic fluency and stigma. The results of this study warrant further therapeutic investigations in PD and provide safety and feasibility data for plasma therapy in people with PD who may be at higher risk for severe complications of COVID‐19. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC. on behalf of International Parkinson and Movement Disorder Society.

Published
2020
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2. Lack of progression of beta dynamics after long‐term subthalamic neurostimulation

Author

Zack Blumenfeld, Emma J. Quinn, Raumin S. Neuville, Jordan E. Parker, Matthew N. Petrucci, Anca Velisar, Declan Cassini, Megan H. Trager, Kevin B. Wilkins, Jaimie M. Henderson, Helen Bronte-Stewart, Ross W. Anderson, Yasmine M. Kehnemouyi, and Mandy Miller Koop

Subjects
Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Deep Brain Stimulation, Neurosciences. Biological psychiatry. Neuropsychiatry, Local field potential, Beta band, Microelectrode recording, Physical medicine and rehabilitation, Subthalamic Nucleus, Outcome Assessment, Health Care, medicine, Clinical endpoint, Humans, RC346-429, Beta (finance), Neurostimulation, Research Articles, Aged, Resting state fMRI, business.industry, General Neuroscience, Subthalamic nucleus deep brain stimulation, Parkinson Disease, Middle Aged, nervous system diseases, Alpha Rhythm, Implantable Neurostimulators, surgical procedures, operative, nervous system, Disease Progression, Neurology. Diseases of the nervous system, Neurology (clinical), business, Beta Rhythm, RC321-571, Research Article, Follow-Up Studies
Abstract

Objective. To investigate the progression of neural and motor features of Parkinson's disease in a longitudinal study, after washout of medication and bilateral subthalamic nucleus deep brain stimulation (STN DBS). Methods. Participants with clinically established Parkinson's disease underwent bilateral implantation of DBS leads (18 participants, 13 male) within the STN using standard functional frameless stereotactic technique and multi-pass microelectrode recording. Both DBS leads were connected to an implanted investigative sensing neurostimulator (Activa™ PC + S, Medtronic, PLC). Resting state STN local field potentials (LFPs) were recorded and motor disability, (the Movement Disorder Society-Unified Parkinson's Disease Rating Scale – motor subscale, MDS-UPDRS III) was assessed off therapy at initial programming, and after 6 months, 1 year, and yearly out to 5 years of treatment. The primary endpoint was measured at 3 years. At each visit, medication had been held for over 12/24 h and DBS was turned off for at least 60 min, by which time LFP spectra reached a steady state. Results. After 3 years of chronic DBS, there were no increases in STN beta band dynamics (p = 0.98) but there were increases in alpha band dynamics (p = 0.0027, 25 STNs). Similar results were observed in a smaller cohort out to 5 years. There was no increase in the MDS-UPDRS III score. Interpretation. These findings provide evidence that the beta oscillopathy does not substantially progress following combined STN DBS plus medication in moderate to advanced Parkinson's disease.

Published
2021

3. Role and evolution of viral tropism in patients with advanced HIV disease receiving intensified initial regimen in the ANRS 130 APOLLO trial

Author

S. Couffin-Cadiergues, Delphine Bonnet, C Merle de Boever, J. M. Livrozet, S. Ben Abdallah, Patrick Yeni, D. Makhloufi, N. El Alami Talbi, M. P. Drogoul, R. Dhote, Daniel Vittecoq, B. C. Phung, N. Benmakhlouf, S Ferrando, S Breaud, F Touam, G. Melica, Pierre Tattevin, Faouzi Souala, C. Augustin-Normand, S. Wassoumbou, F. Sanderson, I. Suaud, P. De Truchis, Jean-Claude Melchior, P. Guadagnin, D. Neau, S. Pavel, B. Warde, O. Taulera, J. Durant, B. Liauthaud, V. Gueripel, P. Sellier, C. Leport, J. L. Touraine, Sophie Leautez-Nainville, N. de Castro, M. A. Arthus, A. Rachline, S. Neuville, Charlotte Charpentier, Sophie Abgrall, M. Bonmarchand, E Aïssi, J. M. Ragnaud, J. F. Faucher, Pascal Pugliese, G. Le Facher, C. Bechara, François Raffi, L. Iordache, O. Derradji, Sophie Tabuteau, A. Frosch, François Bricaire, M. C. Pertusa, J. G. Fuzibet, Y. Mouton, S. Dominguez, P. Dion, I Perbost, Lorraine Letranchant, Jean-François Delfraissy, F. De Salvador, T. Kandel, V. Joly, C. Lascoux-Combe, Cécile Goujard, David Rey, Sylvie Radenne, Michel Dupon, Marc-Antoine Valantin, S. Stegman, F. Bastides, A Brunet, H. Aumaître, M. Lafaurie, V. Reliquet, Christine Katlama, H. Gros, R. Mansouri, J. Delgado, E. Rosenthal, J. Rivalain, G. Pialloux, Cédric Arvieux, David Boutoille, S. Gallien, G. Lepeu, S. Ferret, T. May, M. Parrinello, M. Bentata, Jean-François Bergmann, O. Aubry, J. M. Besnier, Christian Trepo, M. Vassalo, H. Kouadio, Olivier Lortholary, Jean-Albert Gastaut, H. Cordel, H. Dutronc, V. Rahelinirina, P. Lack, Jade Ghosn, Catherine Fagard, J. F. Dailloux, S. Boucherit, P. Honoré-Berlureau, J. M. Chennebault, T. Tahi, Yazdan Yazdanpanah, I. Louis, P. Le Bret, J. M. Estavoyer, J. J. Laurichesse, V. Rabier, I. Schlienger, O. Danne, Jean-Michel Molina, Bruno Hoen, B. Lebouché, Louis Bernard, D. Le, E. Peyrouse, I. Raymond, A. Gervais, Benoit Visseaux, L. Blum, C. Fontaine, Christine Burty, Y Quertainmont, M. Poupard, S Bouchez, J. J. Jourdain, C Cheneau, H. Castillo, Eric Billaud, J. M. Lang, André Cabié, A. Soufflet, J. M. Chapplain, O. Mounoury, B. Bonnet, D. Salmon-Ceron, P. Jouve, V. Mondain, P. Nau, I. Fournier, F. Bailly, J. M. Jacquet, N. Colin de Verdière, C Biron, P. Chiarello, D. Sereni, S. Pierre François, G. Fabre, Juliette Pavie, Lucile Larrouy, F. Rouges, Nathalie Colin de Verdiere, A. Rami, T. Lukiana, M. Maynard, P. Miailhes, J. Delaune, P. Abgueguen, A. Sobel, M. Revest, Clotilde Allavena, S. Herson, Olivier Bouchaud, M. Malet, H. Hüe, M. Iguertsira, A. Leplatois, Jean-Paul Viard, A. Simon, Pierre Dellamonica, Isabelle Poizot-Martin, J. Loison, E. Teicher, M. Lagrange, K. Koffi, E. Pichard, Diane Descamps, M. Ratajczak, Christian Michelet, Loïc Guillevin, A. Krivitzky, W. Kamouh, C. Chesnel, Laurence Slama, J. Cailhol, M. Partisani, N. Agher, Luminita Schneider, S. Boucly, Y. Levy, Laurent Boyer, Jacques Reynes, A. Diallo, M. Môle, N. Bennamar, Laurent Cotte, F. Brunel-Delmas, Philippe Morlat, V. Thoirain, A Foltzer, Laurent Hustache-Mathieu, H. Berthé, Jean-Daniel Lelièvre, C. Tramoni, P. Yeni, Philippe Van de Perre, M. Gory, C. Brunet-François, W. Rozenbaum, M. Saada, Christian Perronne, M. Medus, C. Chakvetadze, T. Huynh, C. Pintado, G. Pahlavan, J. L. Esnault, J. Clarissou, D. Radia, V. Frixon-Marin, E. Boulanger, F. Jeanblanc, P. Choutet, C Ceppi, V. Prendki, Sylvie Abel, Véronique Joly, A. Certain, G. Pichancourt, V. Beaujolais, O. Faucher, C Brochier, Diane Ponscarme, P. Fischer, Aurélie Beuscart, Hugues Melliez, Laboratoire de Virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de maladies infectieuses et tropicales, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de maladies infectieuses et tropicales [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Maladies infectieuses et tropicales, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), ANRS 130 APOLLO Trial Study Group, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)

Subjects
Enfuvirtide, enfuvirtide, MESH: HIV Envelope Protein gp41, viruses, HIV Infections, Drug resistance, MESH: Antiretroviral Therapy, Highly Active, law.invention, MESH: HIV-1, Randomized controlled trial, law, Antiretroviral Therapy, Highly Active, Genotype, Pharmacology (medical), MESH: Anti-HIV Agents, MESH: Peptide Fragments, MESH: Evolution, Molecular, MESH: Aged, 0303 health sciences, MESH: Middle Aged, MESH: Drug Resistance, Viral, tropism, MESH: HIV Infections, Middle Aged, HIV Envelope Protein gp41, switch, 3. Good health, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Young Adult, medicine.drug, Adult, Microbiology (medical), Adolescent, Anti-HIV Agents, Mutation, Missense, Biology, Evolution, Molecular, resistance, Young Adult, 03 medical and health sciences, HIV DNA, Drug Resistance, Viral, medicine, Humans, In patient, Tropism, Aged, 030304 developmental biology, Pharmacology, MESH: Adolescent, MESH: Mutation, Missense, MESH: Humans, 030306 microbiology, MESH: Adult, Virology, Peptide Fragments, Viral Tropism, Regimen, HIV-1, Tissue tropism, MESH: Viral Tropism
Abstract

International audience; OBJECTIVES: The aims of the study were to assess in patients with advanced HIV disease receiving antiretroviral therapy (ART) intensification with enfuvirtide (i) resistance at virological failure (VF), (ii) impact of baseline tropism on immunovirological response, and (iii) HIV-1 DNA tropism evolution during ART. METHODS: The ANRS 130 APOLLO randomized trial evaluated in naive patients the immunovirological impact of standard ART without (control arm) or with enfuvirtide. Tropism was determined on RNA and DNA by V3-loop sequencing interpreted using the Geno2Pheno algorithm. RESULTS: At baseline the median CD4 cell count was 30 cells/mm(3). Among the 170 patients assessable in this virological substudy, HIV-1 RNA tropism was as follows: 60% of viruses were R5 and 40% were R5X4/X4. HIV-1 DNA tropism was as follows: 54% were R5 and 46% were R5X4/X4. At week 24, 39% and 49% of patients experienced VF in the enfuvirtide and control arms, respectively. In the enfuvirtide arm, only resistance-associated mutations to enfuvirtide were detected. In the control arm, two patients displayed drug-resistant viruses at the time of VF. No impact of baseline tropism was observed on immunovirological response, regardless of the study arm. Among the 25 patients experiencing DNA tropism switch between baseline and week 24, 16 (64%) switched from R5 to R5X4/X4. These latter were mostly successfully suppressed patients receiving enfuvirtide and exhibiting poorer immunological response. CONCLUSIONS: Baseline RNA tropism had no impact on the immunovirological response. Drug resistance mutations were only detected for the fusion inhibitor. Finally, the mechanism of replenishment of the viral cellular reservoir with X4 viruses observed needs to be further analysed.

Published
2013
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