المؤلفون: Glenn Carrington, Abbi Hau, Sarah Kosta, Hannah F. Dugdale, Francesco Muntoni, Adele D’Amico, Peter Van den Bergh, Norma B. Romero, Edoardo Malfatti, Juan Jesus Vilchez, Anders Oldfors, Sander Pajusalu, Katrin Õunap, Marta Giralt-Pujol, Edmar Zanoteli, Kenneth S. Campbell, Hiroyuki Iwamoto, Michelle Peckham, Julien Ochala

المصدر: JCI Insight, Vol 8, Iss 21 (2023)

مصطلحات موضوعية: Muscle biology, Medicine

الوصف: Myosin heavy chains encoded by MYH7 and MYH2 are abundant in human skeletal muscle and important for muscle contraction. However, it is unclear how mutations in these genes disrupt myosin structure and function leading to skeletal muscle myopathies termed myosinopathies. Here, we used multiple approaches to analyze the effects of common MYH7 and MYH2 mutations in the light meromyosin (LMM) region of myosin. Analyses of expressed and purified MYH7 and MYH2 LMM mutant proteins combined with in silico modeling showed that myosin coiled coil structure and packing of filaments in vitro are commonly disrupted. Using muscle biopsies from patients and fluorescent ATP analog chase protocols to estimate the proportion of myosin heads that were super-relaxed, together with x-ray diffraction measurements to estimate myosin head order, we found that basal myosin ATP consumption was increased and the myosin super-relaxed state was decreased in vivo. In addition, myofiber mechanics experiments to investigate contractile function showed that myofiber contractility was not affected. These findings indicate that the structural remodeling associated with LMM mutations induces a pathogenic state in which formation of shutdown heads is impaired, thus increasing myosin head ATP demand in the filaments, rather than affecting contractility. These key findings will help design future therapies for myosinopathies.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2379-3708Test

الوصول الحر: https://doaj.org/article/59ff4fd339fd4cbaa9a588a2470f9192Test

المؤلفون: Danique Beijer, Hong Joo Kim, Lin Guo, Kevin O’Donovan, Inès Mademan, Tine Deconinck, Kristof Van Schil, Charlotte M. Fare, Lauren E. Drake, Alice F. Ford, Andrzej Kochański, Dagmara Kabzińska, Nicolas Dubuisson, Peter Van den Bergh, Nicol C. Voermans, Richard J.L.F. Lemmers, Silvère M. van der Maarel, Devon Bonner, Jacinda B. Sampson, Matthew T. Wheeler, Anahit Mehrabyan, Steven Palmer, Peter De Jonghe, James Shorter, J. Paul Taylor, Jonathan Baets

المصدر: JCI Insight, Vol 6, Iss 14 (2021)

مصطلحات موضوعية: Genetics, Neuroscience, Medicine

الوصف: Mutations in HNRNPA1 encoding heterogeneous nuclear ribonucleoprotein (hnRNP) A1 are a rare cause of amyotrophic lateral sclerosis (ALS) and multisystem proteinopathy (MSP). hnRNPA1 is part of the group of RNA-binding proteins (RBPs) that assemble with RNA to form RNPs. hnRNPs are concentrated in the nucleus and function in pre-mRNA splicing, mRNA stability, and the regulation of transcription and translation. During stress, hnRNPs, mRNA, and other RBPs condense in the cytoplasm to form stress granules (SGs). SGs are implicated in the pathogenesis of (neuro-)degenerative diseases, including ALS and inclusion body myopathy (IBM). Mutations in RBPs that affect SG biology, including FUS, TDP-43, hnRNPA1, hnRNPA2B1, and TIA1, underlie ALS, IBM, and other neurodegenerative diseases. Here, we characterize 4 potentially novel HNRNPA1 mutations (yielding 3 protein variants: *321Eext*6, *321Qext*6, and G304Nfs*3) and 2 known HNRNPA1 mutations (P288A and D262V), previously connected to ALS and MSP, in a broad spectrum of patients with hereditary motor neuropathy, ALS, and myopathy. We establish that the mutations can have different effects on hnRNPA1 fibrillization, liquid-liquid phase separation, and SG dynamics. P288A accelerated fibrillization and decelerated SG disassembly, whereas *321Eext*6 had no effect on fibrillization but decelerated SG disassembly. By contrast, G304Nfs*3 decelerated fibrillization and impaired liquid phase separation. Our findings suggest different underlying pathomechanisms for HNRNPA1 mutations with a possible link to clinical phenotypes.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2379-3708Test

الوصول الحر: https://doaj.org/article/47cf72fa59a4478a90634b78aa5718fdTest

المؤلفون: Vincent Tiffreau, Christine Detrembleur, Peter Van Den Bergh, Anne Renders, Virginie Kinet, André Thevenon, Etienne Allart, Thierry Lejeune

المصدر: The Journal of the International Society of Physical and Rehabilitation Medicine, Vol 1, Iss 2, Pp 65-71 (2018)

مصطلحات موضوعية: electromyography, gait analysis, kinematics, kinetics, myotonic dystrophy type 1, treadmill, Orthopedic surgery, RD701-811, Medicine

الوصف: Objective: The objective was to characterize the gait abnormalities in myotonic dystrophy type 1 patients. Material and Methods: Outcomes variables were kinematic and kinetic parameters, timing of muscles, mechanical work and energy cost, and the motor function measure. Results: Despite a high cadence and a low ankle range of motion ratio, ankle extension power, and first extension moment of the knee during the stance, the mechanical work and energy cost were normal. The duration of electromyography activation of the gastrocnemius lateralis (GL) muscle was abnormally long. Conclusion: The hypothesis of a myotonic activity of the GL during the swing phase should be investigated.

وصف الملف: electronic resource

العلاقة: http://www.jisprm.org/article.asp?issn=2349-7904;year=2018;volume=1;issue=2;spage=65;epage=71;aulast=TiffreauTest; https://doaj.org/toc/2589-9457Test

الوصول الحر: https://doaj.org/article/c872e31f3eff4be28fdd84e0816886f8Test

المؤلفون: Carina Bunschoten, Pieter A. van Doorn, Bart C. Jacobs, David R. Cornblath, Luis Querol, Peter Van den Bergh

المساهمون: Neurology, Immunology

المصدر: Journal of the Peripheral Nervous System, 25, 4-8. Wiley-Blackwell Publishing Ltd

مصطلحات موضوعية: medicine.medical_specialty, Polyradiculoneuropathy, Chronic Inflammatory Demyelinating, business.industry, General Neuroscience, medicine, MEDLINE, Humans, Polyradiculoneuropathy, Syndrome, Neurology (clinical), medicine.disease, business, Dermatology

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ff39f4560400b64fc3f7d08bbe2bafeeTest
https://doi.org/10.1111/jns.12364Test

المؤلفون: Bart C. Jacobs, Pieter A. van Doorn, Peter Van den Bergh, Carina Bunschoten, David R. Cornblath

المساهمون: UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service de neurologie, Neurology, Immunology

المصدر: The Lancet. Neurology, Vol. 18, no. 8, p. 784-794 (2019)
Lancet Neurology, 18(8), 784-794. Lancet Publishing Group

مصطلحات موضوعية: 0301 basic medicine, medicine.medical_specialty, Future studies, Nerve ultrasound, Disease, Subcutaneous immunoglobulin, 03 medical and health sciences, 0302 clinical medicine, Adrenal Cortex Hormones, Immunoglobulin g4, medicine, Humans, Intensive care medicine, Plasma Exchange, Treatment regimen, business.industry, Immunoglobulins, Intravenous, Polyradiculoneuropathy, medicine.disease, Treatment Outcome, 030104 developmental biology, Polyradiculoneuropathy, Chronic Inflammatory Demyelinating, Neurology (clinical), business, 030217 neurology & neurosurgery, After treatment

الوصف: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare and heterogeneous but treatable immune-mediated neuropathy. Nerve conduction studies are considered essential for a definite diagnosis, but poor performance and misinterpretation of the results frequently leads to misdiagnosis. Nerve ultrasound and MRI could be helpful in diagnosis. Whereas typical CIDP is relatively easy to diagnose, atypical variants with distinct phenotypes can be a diagnostic challenge. Intravenous or subcutaneous immunoglobulin, corticosteroids, and plasma exchange are effective treatments, but maintenance treatments are often required for years, and treatment regimens require careful and regular adjustments to avoid undertreatment or overtreatment. Patients who do not improve, or insufficiently improve after treatment, might have specific characteristics related to a distinct disease mechanism caused by immunoglobulin G4 antibodies to nodal or paranodal proteins, and could require alternative treatments. Future studies should focus on curative and individualised treatment regimens to improve the patient's condition and to prevent further nerve damage.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c03562102041e48b98e68f5555bc0d84Test
https://doi.org/10.1016/s1474-4422Test(19)30144-9

المؤلفون: Maxwell S. Damian, Lori Renna Linton, Lucia Pavlakova, Claudio L. Bassetti, Maurizio Leone, Thomas Berger, Antonio Toscano, Günther Deuschl, Massimiliano Copetti, Costanza Lamperti, Georg Zimmermann, Johann Sellner, Eugene Trinka, Teia Kobulashvili, Katina Aleksovska, Antonio Federico, Fusun Erdogan, Alessandra Fanciulli, Marianne de Visser, Jean-Marc Burgunder, Martin Rakusa, Luca Vignatelli, Carola Reinhard, Norbert Kovács, Ségolène Aymé, João Costa, Svetlana Kopishinskaya, Peter Van den Bergh, Karen Ritchie, Holm Graessner, Marie Vidailhet, Serenella Servidei, Christian Krarup, Davide Pareyson, Theresina Evangelista

مصطلحات موضوعية: Clinical Practice, medicine.medical_specialty, Neurology, business.industry, Medicine, Neurology (clinical), business, Intensive care medicine

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::baabab69bc6214e337c53c587b4253ebTest
https://avesis.erciyes.edu.tr/publication/details/57242475-0f20-4a25-99be-47c6bd07c1a2/oaiTest

المؤلفون: Inès Mademan, Lauren E. Drake, James Shorter, Kevin J. O'Donovan, Alice Flynn Ford, Andrzej Kochański, Matthew T. Wheeler, Kristof Van Schil, Nicolas Dubuisson, Richard J.L.F. Lemmers, Silvère M. van der Maarel, Jonathan Baets, Devon Bonner, J. Paul Taylor, Peter De Jonghe, Tine Deconinck, Jacinda B. Sampson, Charlotte M. Fare, Anahit Mehrabyan, Peter Van den Bergh, Nicol C. Voermans, Dagmara Kabzińska, Lin Guo, Steven Palmer, Danique Beijer, Hong Joo Kim

المساهمون: UCL - (SLuc) Service de neurologie, UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition, UCL - (SLuc) Centre de référence neuromusculaire

المصدر: Jci Insight, 6, 14
JCI Insight, 6(14). AMER SOC CLINICAL INVESTIGATION INC
JCI Insight
JCI insight, Vol. 6, no.14, p. 1-18 (2021)
Jci Insight, 6
JCI insight

مصطلحات موضوعية: Adult, Male, Heterozygote, TIA1, Heterogeneous nuclear ribonucleoprotein, Adolescent, Heterogeneous Nuclear Ribonucleoprotein A1, DNA Mutational Analysis, Biology, Whole Exome Sequencing, Muscular Atrophy, Spinal, Young Adult, Stress granule, All institutes and research themes of the Radboud University Medical Center, Exome Sequencing, medicine, Genetics, Humans, Amyotrophic lateral sclerosis, Child, Genetic Association Studies, Amyotrophic Lateral Sclerosis, RNA, Translation (biology), General Medicine, Middle Aged, medicine.disease, Cell stress, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Phenotype, Stress Granules, Cell biology, Pedigree, Chemistry, RNA splicing, Mutation, Female, Human medicine, Neurological disorders, Research Article, Neuroscience

الوصف: Mutations in HNRNPA1 encoding heterogeneous nuclear ribonucleoprotein (hnRNP) A1 are a rare cause of amyotrophic lateral sclerosis (ALS) and multisystem proteinopathy (MSP). hnRNPA1 is part of the group of RNA-binding proteins (RBPs) that assemble with RNA to form RNPs. hnRNPs are concentrated in the nucleus and function in pre-mRNA splicing, mRNA stability, and the regulation of transcription and translation. During stress, hnRNPs, mRNA, and other RBPs condense in the cytoplasm to form stress granules (SGs). SGs are implicated in the pathogenesis of (neuro-)degenerative diseases, including ALS and inclusion body myopathy (IBM). Mutations in RBPs that affect SG biology, including FUS, TDP-43, hnRNPA1, hnRNPA2B1, and TIA1, underlie ALS, IBM, and other neurodegenerative diseases. Here, we characterize 4 potentially novel HNRNPA1 mutations (yielding 3 protein variants: *321Eext*6, *321Qext*6, and G304Nfs*3) and 2 known HNRNPA1 mutations (P288A and D262V), previously connected to ALS and MSP, in a broad spectrum of patients with hereditary motor neuropathy, ALS, and myopathy. We establish that the mutations can have different effects on hnRNPA1 fibrillization, liquid-liquid phase separation, and SG dynamics. P288A accelerated fibrillization and decelerated SG disassembly, whereas *321Eext*6 had no effect on fibrillization but decelerated SG disassembly. By contrast, G304Nfs*3 decelerated fibrillization and impaired liquid phase separation. Our findings suggest different underlying pathomechanisms for HNRNPA1 mutations with a possible link to clinical phenotypes.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7f44f7da41fba7d5d08ec3934beb42a6Test
https://hdl.handle.net/1887/3214438Test

المؤلفون: Louise Deldicque, Cheryl Elizabeth Hickmann, Pierre-François Laterre, Marc Francaux, Jean Roeseler, Diego Castanares-Zapatero, Peter Van den Bergh, Gilles Caty, Annie Robert

المصدر: Critical Care Medicine

مصطلحات موضوعية: muscle atrophy, Male, autophagy, early mobilization, medicine.medical_specialty, critically ill, Catabolic state, Clinical Investigations, Critical Care and Intensive Care Medicine, Muscle mass, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Secondary Prevention, medicine, Humans, Muscle, Skeletal, Physical Therapy Modalities, Secondary prevention, business.industry, Septic shock, catabolism, Skeletal muscle, 030208 emergency & critical care medicine, Middle Aged, medicine.disease, Shock, Septic, medicine.anatomical_structure, 030228 respiratory system, Shock (circulatory), ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Physical therapy, septic shock, Female, medicine.symptom, business

الوصف: Supplemental Digital Content is available in the text.
Objectives: As the catabolic state induced by septic shock together with the physical inactivity of patients lead to the rapid loss of muscle mass and impaired function, the purpose of this study was to test whether an early physical therapy during the onset of septic shock regulates catabolic signals and preserves skeletal muscle mass. Design: Randomized controlled trial. Setting: Tertiary mixed ICU. Patients: Adult patients admitted for septic shock within the first 72 hours. Interventions: Patients were assigned randomly into two groups. The control group benefited from manual mobilization once a day. The intervention group had twice daily sessions of both manual mobilization and 30-minute passive/active cycling therapy. Measurements and Main Results: Skeletal muscle biopsies and electrophysiology testing were performed at day 1 and day 7. Muscle biopsies were analyzed for histology and molecular components of signaling pathways regulating protein synthesis and degradation as well as inflammation markers. Hemodynamic values and patient perception were collected during each session. Twenty-one patients were included. Three died before the second muscle biopsy. Ten patients in the control and eight in the intervention group were analyzed. Markers of the catabolic ubiquitin-proteasome pathway, muscle atrophy F-box and muscle ring finger-1 messenger RNA, were reduced at day 7 only in the intervention group, but without difference between groups (muscle atrophy F-box: –7.3% ± 138.4% in control vs –56.4% ± 37.4% in intervention group; p = 0.23 and muscle ring finger-1: –30.8% ± 66.9% in control vs –62.7% ± 45.5% in intervention group; p = 0.15). Muscle fiber cross-sectional area (µm2) was preserved by exercise (–25.8% ± 21.6% in control vs 12.4% ± 22.5% in intervention group; p = 0.005). Molecular regulations suggest that the excessive activation of autophagy due to septic shock was lower in the intervention group, without being suppressed. Markers of anabolism and inflammation were not modified by the intervention, which was well tolerated by the patients. Conclusions: Early physical therapy during the first week of septic shock is safe and preserves muscle fiber cross-sectional area.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1ffa5b41e45a01e22968412e6a7c9c1aTest
https://doi.org/10.1097/ccm.0000000000003263Test

المؤلفون: Anna Sarkozy, Erik-Jan Kamsteeg, Mark Pfuhl, Nicol C. Voermans, Martin Rees, Corrie E. Erasmus, Hülya-Sevcan Daimagüler, Steven A. Moore, Rahul Phadke, Mark R. Holt, Rolf Schröder, Istvan Bodi, Carla Grosmann, Sebahattin Cirak, E. Matthews, Ay Lin Kho, Peter Van den Bergh, Christian Thiel, Shane McKee, Joel Victor Fluss, Roksana Nikoopour, Charu Deshpande, Jens Reimann, Emily C. Oates, Maria Elena Farrugia, Özkan Özdemir, Isabelle Richard, Cristina Domínguez-González, Chaminda Konersman, Ekkehard Wilichowski, Birgit Brandmeier, Atsushi Fukuzawa, Ana Ferreiro, Heinz Jungbluth, Ros Quinlivan, Sandya Tirupathi, Mathias Gautel, Gabriele Dekomien, Cheryl Longman, Miguel A Fernandez-Garcia, Francesco Muntoni, Michael G. Hanna, Elizabeth Wraige, Elke Hobbiebrunken, Sarah Grover

المساهمون: UCL - SSS/IONS - Institute of NeuroScience, UCL - (SLuc) Service de neurologie, UCL - (SLuc) Centre de référence neuromusculaire, King‘s College London, Evelina London Children's Hospital, Guy's Hospital [London], University of Cologne, Children’s University Hospital of Geneva [Switzerland], Queen Elizabeth University Hospital (Glasgow), National Hospital for Neurology and Neurosurgery [London, UK], Great Ormond Street Hospital for Children [London] (GOSH), University College of London [London] (UCL), University of New South Wales [Sydney] (UNSW), Westmead Hospital [Sydney], University Hospital Erlangen [Germany], Universitätsklinikum Erlangen [Erlangen], University of Bonn Medical Centre [Bonn], Radboud university [Nijmegen], Rady Children's Hospital, Belfast City Hospital, Royal Belfast Hospital for Sick Children, University of Iowa [Iowa City], University of Göttingen - Georg-August-Universität Göttingen, Approches génétiques intégrées et nouvelles thérapies pour les maladies rares (INTEGRARE), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Généthon, Généthon, Saint-Luc University Hospital [Brussels, Belgium], Hospital Universitario 12 de Octubre [Madrid], Université de Paris (UP), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), King's College Hospital (KCH), MRC Centre for Neuromuscular Diseases [London, UK], University Hospital Erlangen = Uniklinikum Erlangen, Radboud University [Nijmegen], Radboud University Medical Center [Nijmegen], Gillette Children's Specialty Healthcare [St Paul], Georg-August-University = Georg-August-Universität Göttingen, Ruhr-Universität Bochum [Bochum], Université Paris Cité (UPCité), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)

المصدر: Acta Neuropathologica, 141, 431-453
Acta Neuropathologica, Vol. 141, no. 3, p. 431-453 (2021)
Acta Neuropathologica, 141, 3, pp. 431-453
Acta Neuropathologica
Acta Neuropathologica, Springer Verlag, 2021, 141 (3), pp.431-453. ⟨10.1007/s00401-020-02257-0⟩
Acta Neuropathologica, 2021, 141 (3), pp.431-453. ⟨10.1007/s00401-020-02257-0⟩

مصطلحات موضوعية: Adult, Male, 0301 basic medicine, Weakness, Adolescent, Myotonia Congenita, Mutation, Missense, Other Research Donders Center for Medical Neuroscience [Radboudumc 0], Extraocular muscles, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], Pathology and Forensic Medicine, Young Adult, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Humans, Medicine, Missense mutation, Connectin, Child, Myopathy, Aged, Muscle contracture, Genetics, Phenocopy, Original Paper, biology, business.industry, Infant, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Middle Aged, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], medicine.disease, Congenital myopathy, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Child, Preschool, biology.protein, Female, Titin, Neurology (clinical), medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery

الوصف: Mutations in the sarcomeric protein titin, encoded byTTN, are emerging as a common cause of myopathies. The diagnosis of aTTN-related myopathy is, however, often not straightforward due to clinico-pathological overlap with other myopathies and the prevalence ofTTNvariants in control populations. Here, we present a combined clinico-pathological, genetic and biophysical approach to the diagnosis ofTTN-related myopathies and the pathogenicity ascertainment ofTTNmissense variants. We identified 30 patients with a primaryTTN-related congenital myopathy (CM) and two truncating variants, or one truncating and one missenseTTNvariant, or homozygous for oneTTNmissense variant. We found that TTN-related myopathies show considerable overlap with other myopathies but are strongly suggested by a combination of certain clinico-pathological features. Presentation was typically at birth with the clinical course characterized by variable progression of weakness, contractures, scoliosis and respiratory symptoms but sparing of extraocular muscles. Cardiac involvement depended on the variant position. Our biophysical analyses demonstrated that missense mutations associated with CMs are strongly destabilizing and exert their effect when expressed on a truncating background or in homozygosity. We hypothesise that destabilizingTTNmissense mutations phenocopy truncating variants and are a key pathogenic feature of recessive titinopathies that might be amenable to therapeutic intervention.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a50b0834b2069a16869cd3b6e7cc432fTest
http://hdl.handle.net/2066/231686Test

المؤلفون: H. Stephan Goedee, Thierry Kuntzer, Shahram Attarian, Yusuf A. Rajabally, Peter Van den Bergh

المساهمون: UCL - SSS/IONS - Institute of NeuroScience, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service de neurologie

المصدر: Journal of neurology, neurosurgery, and psychiatry, Vol. 92, no.9, p. 975-982 (2021)

مصطلحات موضوعية: medicine.medical_specialty, Iatrogenic Disease, systematic reviews, Context (language use), Neuropathology, 03 medical and health sciences, 0302 clinical medicine, Immune system, Intervention (counseling), Epidemiology, Medicine, Humans, Intensive care medicine, business.industry, Peripheral Nervous System Diseases, Causality, Clinical Practice, Psychiatry and Mental health, Systematic review, Immune System Diseases, neurotoxicology, 030220 oncology & carcinogenesis, Surgery, neuropathy, Neurology (clinical), neuromuscular, business, 030217 neurology & neurosurgery, guillain-barre syndrome

الوصف: Acute and chronic immune-mediated neuropathies have been widely reported with medical intervention. Although causal relationship may be uncertain in many cases, a variety of drugs, several vaccination types, surgical procedures and bone marrow transplants have been reported as possible cause or trigger of a putative immune-mediated response resulting in acute and chronic neuropathies. We conducted a systematic review of the literature from 1966 to 2020 on reported cases of possible iatrogenic immune-mediated neuropathies. We determined in each case the likelihood of causality based on frequency of the association, focusing primarily on clinical presentation and disease course as well as available ancillary investigations (electrophysiology, blood and cerebrospinal fluid and neuropathology). The response to immunotherapy and issue of re-exposure were also evaluated. We also considered hypothesised mechanisms of onset of immune-mediated neuropathy in the specific iatrogenic context. We believe that a likely causal relationship exists for only few drugs, mainly antitumour necrosis factor alpha agents and immune checkpoint inhibitors, but remains largely unsubstantiated for most other suggested iatrogenic causes. Unfortunately, given the lack of an accurate diagnostic biomarker for most immune-mediated neuropathies, clinical assessment will often override ancillary investigations, resulting in lower levels of certainty that may continue to cast serious doubts on reliability of their diagnosis. Consequently, future reports of suspected cases should collect and exhaustively assess all relevant data. At the current time, besides lack of evidence for causality, the practical implications on management of suspected cases is extremely limited and therapeutic decisions appear likely no different to those made in non-iatrogenic cases.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::339c4a783959dfb334d9ca4858f25d32Test
https://hdl.handle.net/2078.1/264699Test