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2. Guillain-Barré Syndrome Following Zika Virus Infection Is Associated With a Diverse Spectrum of Peripheral Nerve Reactive Antibodies

Author

Davies, Alexander J., Lleixà, Cinta, Siles, Ana M., Gourlay, Dawn S., Berridge, Georgina, Dejnirattisai, Wanwisa, Ramírez-Santana, Carolina, Anaya, Juan-Manuel, Falconar, Andrew K., Romero-Vivas, Claudia M., Osorio, Lyda, Parra, Beatriz, Screaton, Gavin R., Mongkolsapaya, Juthathip, Fischer, Roman, Pardo, Carlos A., Halstead, Susan K., Willison, Hugh J., Querol, Luis, and Rinaldi, Simon

Published
2023
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3. Guillain-Barré syndrome during the Zika virus outbreak in Northeast Brazil: An observational cohort study

Author

Leonhard, Sonja E., Halstead, Susan, Lant, Suzannah B., Militão de Albuquerque, Maria de Fatima Pessoa, de Brito, Carlos Alexandre Antunes, de Albuquerque, Lívia Brito Bezerra, Ellul, Mark A., de Oliveira França, Rafael Freitas, Gourlay, Dawn, Griffiths, Michael J., de Miranda Henriques-Souza, Adélia Maria, de Morais Machado, Maria Í., Medialdea-Carrera, Raquel, Mehta, Ravi, da Paz Melo, Roberta, Mesquita, Solange D., Moreira, Álvaro J.P., Pena, Lindomar J., Santos, Marcela Lopes, Turtle, Lance, Solomon, Tom, Willison, Hugh J., Jacobs, Bart C., and Brito Ferreira, Maria L.

Published
2021
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5. Neurological disease in adults with Zika and chikungunya virus infection in Northeast Brazil: a prospective observational study

Author

Brito Ferreira, Maria Lúcia, Militão de Albuquerque, Maria de Fatima Pessoa, de Brito, Carlos Alexandre Antunes, de Oliveira França, Rafael Freitas, Porto Moreira, Álvaro José, de Morais Machado, Maria Íris, da Paz Melo, Roberta, Medialdea-Carrera, Raquel, Dornelas Mesquita, Solange, Lopes Santos, Marcela, Mehta, Ravi, Ramos e Silva, Rafael, Leonhard, Sonja E, Ellul, Mark, Rosala-Hallas, Anna, Burnside, Girvan, Turtle, Lance, Griffiths, Michael J, Jacobs, Bart C, Bhojak, Maneesh, Willison, Hugh J, Pena, Lindomar José, Pardo, Carlos A, Ximenes, Ricardo A A, Martelli, Celina Maria Turchi, Brown, David W G, Cordeiro, Marli Tenório, Lant, Suzannah, and Solomon, Tom

Published
2020
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6. Predicting Outcome in Guillain-Barré Syndrome: International Validation of the Modified Erasmus GBS Outcome Score

Author

Doets, Alex Y, Lingsma, Hester F, Walgaard, Christa, Islam, Badrul, Papri, Nowshin, Davidson, Amy, Yamagishi, Yuko, Kusunoki, Susumu, Dimachkie, Mazen M, Waheed, Waqar, Kolb, Noah, Islam, Zhahirul, Mohammad, Quazi Deen, Harbo, Thomas, Sindrup, Soren H, Chavada, Govindsinh, Willison, Hugh J, Casasnovas, Carlos, Bateman, Kathleen, Miller, James AL, van den Berg, Bianca, Verboon, Christine, Roodbol, Joyce, Leonhard, Sonja E, Benedetti, Luana, Kuwabara, Satoshi, Van den Bergh, Peter, Monges, Soledad, Marfia, Girolama A, Shahrizaila, Nortina, Galassi, Giuliana, Péréon, Yann, Bürmann, Jan, Kuitwaard, Krista, Kleyweg, Ruud P, Marchesoni, Cintia, Sedano Tous, María J, Querol, Luis, Illa, Isabel, Wang, Yuzhong, Nobile-Orazio, Eduardo, Rinaldi, Simon, Schenone, Angelo, Pardo, Julio, Vermeij, Frederique H, Lehmann, Helmar C, Granit, Volkan, Cavaletti, Guido, Gutiérrez-Gutiérrez, Gerardo, Barroso, Fabio A, Visser, Leo H, Katzberg, Hans D, Dardiotis, Efthimios, Attarian, Shahram, van der Kooi, Anneke J, Eftimov, Filip, Wirtz, Paul W, Samijn, Johnny PA, Gilhuis, H Jacobus, Hadden, Robert DM, Holt, James KL, Sheikh, Kazim A, Karafiath, Summer, Vytopil, Michal, Antonini, Giovanni, Feasby, Thomas E, Faber, Catharina G, Gijsbers, Cees J, Busby, Mark, Roberts, Rhys C, Silvestri, Nicholas J, Fazio, Raffaella, van Dijk, Gert W, Garssen, Marcel PJ, Straathof, Chiara SM, Gorson, Kenneth C, and Jacobs, Bart C

Published
2021
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7. A Novel Cytotoxic Mechanism for Triple-Negative Breast Cancer Cells Induced by the Type II Heat-Labile Enterotoxin LT-IIc through Ganglioside Ligation.

Author

King-Lyons, Natalie D., Bhati, Aryana S., Hu, John C., Mandell, Lorrie M., Shenoy, Gautam N., Willison, Hugh J., and Connell, Terry D.

Subjects
TRIPLE-negative breast cancer, CYTOTOXINS, BREAST cancer, EPITHELIAL cells, CELL death
Abstract

Triple-negative breast cancer (TNBC), which constitutes 10–20 percent of all breast cancers, is aggressive, has high metastatic potential, and carries a poor prognosis due to limited treatment options. LT-IIc, a member of the type II subfamily of ADP-ribosylating—heat-labile enterotoxins that bind to a distinctive set of cell-surface ganglioside receptors—is cytotoxic toward TNBC cell lines, but has no cytotoxic activity for non-transformed breast epithelial cells. Here, primary TNBC cells, isolated from resected human tumors, showed an enhanced cytotoxic response specifically toward LT-IIc, in contrast to other enterotoxins that were tested. MDA-MB-231 cells, a model for TNBC, were used to evaluate potential mechanisms of cytotoxicity by LT-IIc, which induced elevated intracellular cAMP and stimulated the cAMP response element-binding protein (CREB) signaling pathway. To dissect the role of ADP-ribosylation, cAMP induction, and ganglioside ligation in the cytotoxic response, MDA-MB-231 cells were exposed to wild-type LT-IIc, the recombinant B-pentamer of LT-IIc that lacks the ADP-ribosylating A polypeptide, or mutants of LT-IIc with an enzymatically inactivated A1-domain. These experiments revealed that the ADP-ribosyltransferase activity of LT-IIc was nonessential for inducing the lethality of MDA-MB-231 cells. In contrast, a mutant LT-IIc with an altered ganglioside binding activity failed to trigger a cytotoxic response in MDA-MB-231 cells. Furthermore, the pharmacological inhibition of ganglioside expression protected MDA-MB-231 cells from the cytotoxic effects of LT-IIc. These data establish that ganglioside ligation, but not the induction of cAMP production nor ADP-ribosyltransferase activity, is essential to initiating the LT-IIc-dependent cell death of MDA-MB-231 cells. These experiments unveiled previously unknown properties of LT-IIc and gangliosides in signal transduction, offering the potential for the targeted treatment of TNBC, an option that is desperately needed. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Schwann cell nodal membrane disruption triggers bystander axonal degeneration in a Guillain-Barre syndrome mouse model

Author

McGonigal, Rhona, Campbell, Clare I., Barrie, Jennifer A., Yao, Denggao, Cunningham, Madeleine E., Crawford, Colin L., Rinaldi, Simon, Rowan, Edward G., and Willison, Hugh J.

Subjects
Physiological aspects, Models, Development and progression, Risk factors, Injuries, Schwann cells -- Physiological aspects, Gangliosides -- Physiological aspects, Axons -- Injuries, Guillain-Barre syndrome -- Risk factors -- Development and progression -- Models
Abstract

Introduction Guillain-Barre syndrome (GBS) is a postinfectious autoimmune disorder affecting the peripheral nervous system (PNS) resulting in acute-onset paralysis (1). GBS comprises a spectrum of axonal and demyelinating variants that [...], In Guillain-Barre syndrome (GBS), both axonal and demyelinating variants can be mediated by complement-fixing anti-GM1 ganglioside autoantibodies that target peripheral nerve axonal and Schwann cell (SC) membranes, respectively. Critically, the extent of axonal degeneration in both variants dictates long-term outcome. The differing pathomechanisms underlying direct axonal injury and the secondary bystander axonal degeneration following SC injury are unresolved. To investigate this, we generated glycosyltransferase-disrupted transgenic mice that express GM1 ganglioside either exclusively in neurons [[GalNAcT.sup.-/-]-Tg(neuronal)] or glia [[GalNAcT.sup.-/-]-Tg(glial)], thereby allowing anti-GM1 antibodies to solely target GM1 in either axonal or SC membranes, respectively. Myelinated-axon integrity in distal motor nerves was studied in transgenic mice exposed to anti-GM1 antibody and complement in ex vivo and in vivo injury paradigms. Axonal targeting induced catastrophic acute axonal disruption, as expected. When mice with GM1 in SC membranes were targeted, acute disruption of perisynaptic glia and SC membranes at nodes of Ranvier (NoRs) occurred. Following glial injury, axonal disruption at NoRs also developed subacutely, progressing to secondary axonal degeneration. These models differentiate the distinctly different axonopathic pathways under axonal and glial membrane targeting conditions, and provide insights into primary and secondary axonal injury, currently a major unsolved area in GBS research.

Published
2022
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10. Diagnosis and management of Guillain–Barré syndrome in ten steps

Author

Leonhard, Sonja E., Mandarakas, Melissa R., Gondim, Francisco A. A., Bateman, Kathleen, Ferreira, Maria L. B., Cornblath, David R., van Doorn, Pieter A., Dourado, Mario E., Hughes, Richard A. C., Islam, Badrul, Kusunoki, Susumu, Pardo, Carlos A., Reisin, Ricardo, Sejvar, James J., Shahrizaila, Nortina, Soares, Cristiane, Umapathi, Thirugnanam, Wang, Yuzhong, Yiu, Eppie M., Willison, Hugh J., and Jacobs, Bart C.

Published
2019
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11. CSF Findings in Relation to Clinical Characteristics, Subtype, and Disease Course in Patients With Guillain-Barré Syndrome

Author

Al-Hakem, Helle, Doets, Alex Y, Stino, Amro Maher, Zivkovic, Sasha A, Andersen, Henning, Willison, Hugh J, Cornblath, David R, Gorson, Kenneth C, Islam, Zhahirul, Mohammad, Quazi Deen, Sindrup, Søren Hein, Kusunoki, Susumu, Davidson, Amy, Casasnovas, Carlos, Bateman, Kathleen, Miller, James A L, van den Berg, Bianca, Verboon, Christine, Roodbol, Joyce, Leonhard, Sonja E, Arends, Samuel, Luijten, Linda W G, Benedetti, Luana, Kuwabara, Satoshi, Van den Bergh, Peter, Monges, Soledad, Marfia, Girolama A, Shahrizaila, Nortina, Galassi, Giuliana, Pereon, Yann, Bürmann, Jan, Kuitwaard, Krista, Kleyweg, Ruud P, Marchesoni, Cintia, Sedano Tous, María J, Querol, Luis, Martín-Aguilar, Lorena, Wang, Yuzhong, Nobile-Orazio, Eduardo, Rinaldi, Simon, Schenone, Angelo, Pardo, Julio, Vermeij, Frederique H, Waheed, Waqar, Lehmann, Helmar C, Granit, Volkan, Stein, Beth, Samijn, Johnny P A, van Dijk, Gert W, Jacobs, Bart C, Neurology, Medical Microbiology & Infectious Diseases, Public Health, and Immunology

Subjects
Neurology (clinical)
Abstract

BACKGROUND AND OBJECTIVES: To investigate CSF findings in relation to clinical and electrodiagnostic subtypes, severity, and outcome of Guillain-Barré syndrome (GBS) based on 1,500 patients in the International GBS Outcome Study. METHODS: Albuminocytologic dissociation (ACD) was defined as an increased protein level (>0.45 g/L) in the absence of elevated white cell count (4 days 84%. High CSF protein levels were associated with a demyelinating subtype, proximal or global muscle weakness, and a reduced likelihood of being able to run at week 2 (odds ratio [OR] 0.42, 95% CI 0.25-0.70; p = 0.001) and week 4 (OR 0.44, 95% CI 0.27-0.72; p = 0.001). Patients with the Miller Fisher syndrome, distal predominant weakness, and normal or equivocal nerve conduction studies were more likely to have lower CSF protein levels. CSF cell count was

Published
2023

12. European Academy of Neurology/Peripheral Nerve Society Guideline on diagnosis and treatment of Guillain–Barré syndrome

Author

van Doorn, Pieter A., primary, Van den Bergh, Peter Y. K., additional, Hadden, Robert D. M., additional, Avau, Bert, additional, Vankrunkelsven, Patrik, additional, Attarian, Shahram, additional, Blomkwist‐Markens, Patricia H., additional, Cornblath, David R., additional, Goedee, H. Stephan, additional, Harbo, Thomas, additional, Jacobs, Bart C., additional, Kusunoki, Susumu, additional, Lehmann, Helmar C., additional, Lewis, Richard A., additional, Lunn, Michael P., additional, Nobile‐Orazio, Eduardo, additional, Querol, Luis, additional, Rajabally, Yusuf A., additional, Umapathi, Thirugnanam, additional, Topaloglu, Haluk A., additional, and Willison, Hugh J., additional

Published
2023
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14. Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study

Author

Cao-Lormeau, Van-Mai, Blake, Alexandre, Mons, Sandrine, Lastère, Stéphane, Roche, Claudine, Vanhomwegen, Jessica, Dub, Timothée, Baudouin, Laure, Teissier, Anita, Larre, Philippe, Vial, Anne-Laure, Decam, Christophe, Choumet, Valérie, Halstead, Susan K, Willison, Hugh J, Musset, Lucile, Manuguerra, Jean-Claude, Despres, Philippe, Fournier, Emmanuel, Mallet, Henri-Pierre, Musso, Didier, Fontanet, Arnaud, Neil, Jean, and Ghawché, Frédéric

Published
2016
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15. Current treatment practice of Guillain-Barré syndrome

Author

Verboon, Christine, Doets, Alex Y., Galassi, Giuliana, Davidson, Amy, Waheed, Waqar, Péréon, Yann, Shahrizaila, Nortina, Kusunoki, Susumu, Lehmann, Helmar C., Harbo, Thomas, Monges, Soledad, Van den Bergh, Peter, Willison, Hugh J., Cornblath, David R., and Jacobs, Bart C.

Published
2019
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16. European Academy of Neurology/Peripheral Nerve Society Guideline on diagnosis and treatment of Guillain–Barré syndrome

Author

van Doorn, Pieter A., Van den Bergh, Peter Y.K., Hadden, Robert D.M., Avau, Bert, Vankrunkelsven, Patrik, Attarian, Shahram, Blomkwist-Markens, Patricia H., Cornblath, David R., Goedee, H. Stephan, Harbo, Thomas, Jacobs, Bart C., Kusunoki, Susumu, Lehmann, Helmar C., Lewis, Richard A., Lunn, Michael P., Nobile-Orazio, Eduardo, Querol, Luis, Rajabally, Yusuf A., Umapathi, Thirugnanam, Topaloglu, Haluk A., Willison, Hugh J., van Doorn, Pieter A., Van den Bergh, Peter Y.K., Hadden, Robert D.M., Avau, Bert, Vankrunkelsven, Patrik, Attarian, Shahram, Blomkwist-Markens, Patricia H., Cornblath, David R., Goedee, H. Stephan, Harbo, Thomas, Jacobs, Bart C., Kusunoki, Susumu, Lehmann, Helmar C., Lewis, Richard A., Lunn, Michael P., Nobile-Orazio, Eduardo, Querol, Luis, Rajabally, Yusuf A., Umapathi, Thirugnanam, Topaloglu, Haluk A., and Willison, Hugh J.

Abstract

Guillain–Barré syndrome (GBS) is an acute polyradiculoneuropathy. Symptoms may vary greatly in presentation and severity. Besides weakness and sensory disturbances, patients may have cranial nerve involvement, respiratory insufficiency, autonomic dysfunction and pain. To develop an evidence-based guideline for the diagnosis and treatment of GBS, using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology a Task Force (TF) of the European Academy of Neurology (EAN) and the Peripheral Nerve Society (PNS) constructed 14 Population/Intervention/Comparison/Outcome questions (PICOs) covering diagnosis, treatment and prognosis of GBS, which guided the literature search. Data were extracted and summarised in GRADE Summaries of Findings (for treatment PICOs) or Evidence Tables (for diagnostic and prognostic PICOs). Statements were prepared according to GRADE Evidence-to-Decision (EtD) frameworks. For the six intervention PICOs, evidence-based recommendations are made. For other PICOs, good practice points (GPPs) are formulated. For diagnosis, the principal GPPs are: GBS is more likely if there is a history of recent diarrhoea or respiratory infection; CSF examination is valuable, particularly when the diagnosis is less certain; electrodiagnostic testing is advised to support the diagnosis; testing for anti-ganglioside antibodies is of limited clinical value in most patients with typical motor-sensory GBS, but anti-GQ1b antibody testing should be considered when Miller Fisher syndrome (MFS) is suspected; nodal–paranodal antibodies should be tested when autoimmune nodopathy is suspected; MRI or ultrasound imaging should be considered in atypical cases; and changing the diagnosis to acute-onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP) should be considered if progression continues after 8 weeks from onset, which occurs in around 5% of patients initially diagnosed with GBS. For treatment, the TF recommends intravenous

Published
2023

17. Cerebrospinal Fluid Findings in Relation to Clinical Characteristics, Subtype, and Disease Course in Patients With Guillain-Barré Syndrome

Author

Al-Hakem, Helle, primary, Doets, Alex Y, additional, Stino, Amro Maher, additional, Zivkovic, Sasha A., additional, Andersen, Henning, additional, Willison, Hugh J, additional, Cornblath, David R, additional, Gorson, Kenneth C, additional, Islam, Zhahirul, additional, Mohammad, Quazi Deen, additional, Sindrup, Søren Hein, additional, Kusunoki, Susumu, additional, Davidson, Amy, additional, Casasnovas, Carlos, additional, Bateman, Kathleen, additional, Miller, James AL, additional, van den Berg, Bianca, additional, Verboon, Christine, additional, Roodbol, Joyce, additional, Leonhard, Sonja E, additional, Arends, Samuel, additional, Luijten, Linda W G, additional, Benedetti, Luana, additional, Kuwabara, Satoshi, additional, Van den Bergh, Peter, additional, Monges, Soledad, additional, Marfia, Girolama A, additional, Shahrizaila, Nortina, additional, Galassi, Giuliana, additional, Pereon, Yann, additional, Bürmann, Jan, additional, Kuitwaard, Krista, additional, Kleyweg, Ruud P, additional, Marchesoni, Cintia, additional, Sedano Tous, María J, additional, Querol, Luis, additional, Martín-Aguilar, Lorena, additional, Wang, Yuzhong, additional, Nobile-Orazio, Eduardo, additional, Rinaldi, Simon, additional, Schenone, Angelo, additional, Pardo, Julio, additional, Vermeij, Frederique H, additional, Waheed, Waqar, additional, Lehmann, Helmar C, additional, Granit, Volkan, additional, Stein, Beth, additional, Cavaletti, Guido, additional, Gutiérrez-Gutiérrez, Gerardo, additional, Barroso, Fabio A, additional, Visser, Leo H, additional, Katzberg, Hans D, additional, Dardiotis, Efthimios, additional, Attarian, Shahram, additional, van der Kooi, Anneke J, additional, Eftimov, Filip, additional, Wirtz, Paul W, additional, PA Samijn, Johnny, additional, Gilhuis, H Jacobus, additional, DM Hadden, Robert, additional, Holt, James KL, additional, Sheikh, Kazim A, additional, Kolb, Noah, additional, Karafiath, Summer, additional, Vytopil, Michal, additional, Antonini, Giovanni, additional, Feasby, Thomas E, additional, Faber, Catharina, additional, Kramers, Hans, additional, Busby, Mark, additional, Roberts, Rhys C, additional, Silvestri, Nicholas J, additional, Fazio, Raffaella, additional, van Dijk, Gert W, additional, Garssen, Marcel PJ, additional, Verschuuren, Jan, additional, Harbo, Thomas, additional, and Jacobs, Bart C, additional

Published
2023
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22. Serum anti‐GM2 and anti‐GalNAc‐GD1a ganglioside IgG antibodies are biomarkers for immune‐mediated polyneuropathies in cats

Author

Halstead, Susan K., primary, Jackson, Mark, additional, Bianchi, Ezio, additional, Rupp, Stefan, additional, Granger, Nicolas, additional, Menchetti, Marika, additional, Galli, Greta, additional, Freeman, Paul, additional, Kaczmarska, Adriana, additional, Bhatti, Sofie F. M., additional, Brocal, Josep, additional, José‐López, Roberto, additional, Tipold, Andrea, additional, Gutierrez Quintana, Rodrigo, additional, Ives, Edward J., additional, Liatis, Theofanis, additional, Nessler, Jasmin, additional, Rusbridge, Clare, additional, Willison, Hugh J., additional, and Rupp, Angie, additional

Published
2023
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27. Post-Infectious Autoimmunity in the Central (CNS) and Peripheral (PNS) Nervous Systems: An African Perspective

Author

Ndondo, Alvin Pumelele, Eley, Brian, Wilmshurst, Jo Madeleine, Kakooza-Mwesige, Angelina, Giannoccaro, Maria Pia, Willison, Hugh J., Cruz, Pedro M. Rodríguez, Heckmann, Jeannine M., Bateman, Kathleen, Vincent, Angela, Ndondo, Alvin Pumelele, Eley, Brian, Wilmshurst, Jo Madeleine, Kakooza-Mwesige, Angelina, Giannoccaro, Maria Pia, Willison, Hugh J, Cruz, Pedro M Rodríguez, Heckmann, Jeannine M, Bateman, Kathleen, and Vincent, Angela

Subjects
Adult, Central Nervous System, Immunology, Àfrica, Communicable Diseases, COVID-19 (Malaltia), Communicable Disease, encephaliti, Central Nervous System Diseases, peripheral nervous system, Humans, Malalties transmissibles, Immunology and Allergy, neurological disorder, Child, Brain Diseases, post-infectiou, autoimmunity, Brain Disease, COVID-19, Peripheral Nervous System Diseases, encephalopathy, immunity, Sistema nerviós -- Malalties, Immunitat, Central Nervous System Disease, Africa, Encephalitis, Human
Abstract

The direct impact and sequelae of infections in children and adults result in significant morbidity and mortality especially when they involve the central (CNS) or peripheral nervous system (PNS). The historical understanding of the pathophysiology has been mostly focused on the direct impact of the various pathogens through neural tissue invasion. However, with the better understanding of neuroimmunology, there is a rapidly growing realization of the contribution of the innate and adaptive host immune responses in the pathogenesis of many CNS and PNS diseases.The balance between the protective and pathologic sequelae of immunity is fragile and can easily be tipped towards harm for the host. The matter of immune privilege and surveillance of the CNS/PNS compartments and the role of the blood-brain barrier (BBB) and blood nerve barrier (BNB) makes this even more complex. Our understanding of the pathogenesis of many post-infectious manifestations of various microbial agents remains elusive, especially in the diverse African setting. Our exploration and better understanding of the neuroimmunology of some of the infectious diseases that we encounter in the continent will go a long way into helping us to improve their management and therefore lessen the burden.Africa is diverse and uniquely poised because of the mix of the classic, well described, autoimmune disease entities and the specifically “tropical” conditions. This review explores the current understanding of some of the para- and post-infectious autoimmune manifestations of CNS and PNS diseases in the African context. We highlight the clinical presentations, diagnosis and treatment of these neurological disorders and underscore the knowledge gaps and perspectives for future research using disease models of conditions that we see in the continent, some of which are not uniquely African and, where relevant, include discussion of the proposed mechanisms underlying pathogen-induced autoimmunity. This review covers the following conditions as models and highlight those in which a relationship with COVID-19 infection has been reported: a) Acute Necrotizing Encephalopathy; b) Measles-associated encephalopathies; c) Human Immunodeficiency Virus (HIV) neuroimmune disorders, and particularly the difficulties associated with classical post-infectious autoimmune disorders such as the Guillain-Barré syndrome in the context of HIV and other infections. Finally, we describe NMDA-R encephalitis, which can be post-HSV encephalitis, summarise other antibody-mediated CNS diseases and describe myasthenia gravis as the classic antibody-mediated disease but with special features in Africa.

Published
2022
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28. Guillain-Barré Syndrome Following Zika Virus Infection Is Associated With a Diverse Spectrum of Peripheral Nerve Reactive Antibodies

Author

Davies, Alexander J., primary, Lleixà, Cinta, additional, Siles, Ana M., additional, Gourlay, Dawn S., additional, Berridge, Georgina, additional, Dejnirattisai, Wanwisa, additional, Ramírez-Santana, Carolina, additional, Anaya, Juan-Manuel, additional, Falconar, Andrew K., additional, Romero-Vivas, Claudia M., additional, Osorio, Lyda, additional, Parra, Beatriz, additional, Screaton, Gavin R., additional, Mongkolsapaya, Juthathip, additional, Fischer, Roman, additional, Pardo, Carlos A., additional, Halstead, Susan K., additional, Willison, Hugh J., additional, Querol, Luis, additional, and Rinaldi, Simon, additional

Published
2022
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36. SARM1 Depletion Slows Axon Degeneration in a CNS Model of Neurotropic Viral Infection

Author

Crawford, Colin L., Antoniou, Christina, Komarek, Lina, Schultz, Verena, Donald, Claire L., Montague, Paul, Barnett, Susan C., Linington, Christopher, Willison, Hugh J., Kohl, Alain, Coleman, Michael P., Edgar, Julia M., Coleman, Michael [0000-0002-9354-532X], and Apollo - University of Cambridge Repository

Subjects
tubulin (microtubules), Cellular and Molecular Neuroscience, nervous system, glia, neurofilament, nicotinamide adenine dinucleotide, Molecular Biology, Zika virus
Abstract

Zika virus (ZIKV) is a neurotropic flavivirus recently linked to congenital ZIKV syndrome in children and encephalitis and Guillain-Barré syndrome in adults. Neurotropic viruses often use axons to traffic to neuronal or glial cell somas where they either remain latent or replicate and proceed to infect new cells. Consequently, it has been suggested that axon degeneration could represent an evolutionarily conserved mechanism to limit viral spread. Whilst it is not known if ZIKV transits in axons, we previously reported that ZIKV infection of glial cells in a murine spinal cord-derived cell culture model of the CNS is associated with a profound loss of neuronal cell processes. This, despite that postmitotic neurons are relatively refractory to infection and death. Here, we tested the hypothesis that ZIKV-associated degeneration of neuronal processes is dependent on activation of Sterile alpha and armadillo motif-containing protein 1 (SARM1), an NADase that acts as a central executioner in a conserved axon degeneration pathway. To test this, we infected wild type and Sarm1 homozygous or heterozygous null cell cultures with ZIKV and examined NAD+ levels as well as the survival of neurons and their processes. Unexpectedly, ZIKV infection led to a rapid SARM1-independent reduction in NAD+. Nonetheless, the subsequent profound loss of neuronal cell processes was SARM1-dependent and was preceded by early changes in the appearance of β-tubulin III staining. Together, these data identify a role for SARM1 in the pathogenesis of ZIKV infection, which may reflect SARM1's conserved prodegenerative function, independent of its NADase activity.

Published
2022
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37. An International Perspective on Preceding Infections in Guillain-Barre Syndrome The IGOS-1000 Cohort

Author

Leonhard, Sonja E., van der Eijk, Annemiek A., Andersen, Henning, Antonini, Giovanni, Arends, Samuel, Attarian, Shahram, Barroso, Fabio A., Bateman, Kathleen J., Batstra, Manou R., Benedetti, Luana, van den Berg, Bianca, Van den Bergh, Peter, Burmann, Jan, Busby, Mark, Casasnovas, Carlos, Cornblath, David R., Davidson, Amy, Doets, Alex Y., van Doorn, Pieter A., de la Cour, Charlotte Dornonville, Feasby, Thomas E., Fehmi, Janev, Garcia-Sobrino, Tania, Goldstein, Jonathan M., Gorson, Kenneth C., Granit, Volkan, Hadden, Robert D. M., Harbo, Thomas, Hartung, Hans-Peter, Hasan, Imran, Holbech, Jakob, V, Holt, James K. L., Jahan, Israt, Islam, Zhahirul, Karafiath, Summer, Katzberg, Hans D., Kleyweg, Ruud P., Kolb, Noah, Kuitwaard, Krista, Kuwahara, Motoi, Kusunoki, Susumu, Luijten, Linda W. G., Kuwabara, Satoshi, Pan, Edward Lee, Lehmann, Helmar C., Maas, Marijke, Martin-Aguilar, Lorena, Al Miller, James, Mohammad, Quazi Deen, Monges, Soledad, Nedkova-Hristova, Velina, Nobile-Orazio, Eduardo, Pardo, Julio, Pereon, Yann, Querol, Luis, Reisin, Ricardo, Van Rijs, Wouter, Rinaldi, Simon, Roberts, Rhys C., Roodbol, Joyce, Shahrizaila, Nortina, Sindrup, Soren Hein, Stein, Beth, Cheng-Yin, Tan, Tankisi, Hatice, Tio-Gillen, Anne P., Tous, Maria J. Sedano, Verboon, Christine, Vermeij, Frederique H., Visser, Leo H., Huizinga, Ruth, Willison, Hugh J., Jacobs, Bart C., Leonhard, Sonja E., van der Eijk, Annemiek A., Andersen, Henning, Antonini, Giovanni, Arends, Samuel, Attarian, Shahram, Barroso, Fabio A., Bateman, Kathleen J., Batstra, Manou R., Benedetti, Luana, van den Berg, Bianca, Van den Bergh, Peter, Burmann, Jan, Busby, Mark, Casasnovas, Carlos, Cornblath, David R., Davidson, Amy, Doets, Alex Y., van Doorn, Pieter A., de la Cour, Charlotte Dornonville, Feasby, Thomas E., Fehmi, Janev, Garcia-Sobrino, Tania, Goldstein, Jonathan M., Gorson, Kenneth C., Granit, Volkan, Hadden, Robert D. M., Harbo, Thomas, Hartung, Hans-Peter, Hasan, Imran, Holbech, Jakob, V, Holt, James K. L., Jahan, Israt, Islam, Zhahirul, Karafiath, Summer, Katzberg, Hans D., Kleyweg, Ruud P., Kolb, Noah, Kuitwaard, Krista, Kuwahara, Motoi, Kusunoki, Susumu, Luijten, Linda W. G., Kuwabara, Satoshi, Pan, Edward Lee, Lehmann, Helmar C., Maas, Marijke, Martin-Aguilar, Lorena, Al Miller, James, Mohammad, Quazi Deen, Monges, Soledad, Nedkova-Hristova, Velina, Nobile-Orazio, Eduardo, Pardo, Julio, Pereon, Yann, Querol, Luis, Reisin, Ricardo, Van Rijs, Wouter, Rinaldi, Simon, Roberts, Rhys C., Roodbol, Joyce, Shahrizaila, Nortina, Sindrup, Soren Hein, Stein, Beth, Cheng-Yin, Tan, Tankisi, Hatice, Tio-Gillen, Anne P., Tous, Maria J. Sedano, Verboon, Christine, Vermeij, Frederique H., Visser, Leo H., Huizinga, Ruth, Willison, Hugh J., and Jacobs, Bart C.

Abstract

Background and Objectives Infections play a key role in the development of Guillain-Barre syndrome (GBS) and have been associated with specific clinical features and disease severity. The clinical variation of GBS across geographical regions has been suggested to be related to differences in the distribution of preceding infections, but this has not been studied on a large scale. Methods We analyzed the first 1,000 patients included in the International GBS Outcome Study with available biosamples (n = 768) for the presence of a recent infection with Campylobacter jejuni, hepatitis E virus, Mycoplasma pneumoniae, cytomegalovirus, and Epstein-Barr virus. Results Serologic evidence of a recent infection with C. jejuni was found in 228 (30%), M. pneumoniae in 77 (10%), hepatitis E virus in 23 (3%), cytomegalovirus in 30 (4%), and Epstein-Barr virus in 7 (1%) patients. Evidence of more than 1 recent infection was found in 49 (6%) of these patients. Symptoms of antecedent infections were reported in 556 patients (72%), and this proportion did not significantly differ between those testing positive or negative for a recent infection. The proportions of infections were similar across continents. The sensorimotor variant and the demyelinating electrophysiologic subtype were most frequent across all infection groups, although proportions were significantly higher in patients with a cytomegalovirus and significantly lower in those with a C. jejuni infection. C. jejuni-positive patients were more severely affected, indicated by a lower Medical Research Council sum score at nadir (p = 0.004) and a longer time to regain the ability to walk independently (p = 0.005). The pure motor variant and axonal electrophysiologic subtype were more frequent in Asian compared with American or European C. jejuni-positive patients (p < 0.001, resp. p = 0.001). Time to nadir was longer in the cytomegalovirus-positive patients (p = 0.004). Discussion Across geographical regions, the distribution o

Published
2022

38. Predicting Outcome in Guillain-Barre Syndrome International Validation of the Modified Erasmus GBS Outcome Score

Author

Doets, Alex Y., Lingsma, Hester F., Walgaard, Christa, Islam, Badrul, Papri, Nowshin, Davidson, Amy, Kusunoki, Susumu, Dimachkie, Mazen M., Waheed, Waqar, Kolb, Noah, Islam, Zhahirul, Mohammad, Quazi Deen, Harbo, Thomas, Sindrup, Soren H., Chavada, Govindsinh, Willison, Hugh J., Casasnovas, Carlos, Bateman, Kathleen, Miller, James A. L., van den Berg, Bianca, Verboon, Christine, Roodbol, Joyce, Leonhard, Sonja E., Benedetti, Luana, Kuwabara, Satoshi, Van den Bergh, Peter, Monges, Soledad, Marfia, Girolama A., Shahrizaila, Nortina, Galassi, Giuliana, Pereon, Yann, Burmann, Jan, Kuitwaard, Krista, Kleyweg, Ruud P., Marchesoni, Cintia, Tous, Maria J. Sedano, Querol, Luis, Illa, Isabel, Wang, Yuzhong, Nobile-Orazio, Eduardo, Rinaldi, Simon, Schenone, Angelo, Pardo, Julio, Vermeij, Frederique H., Lehmann, Helmar C., Granit, Volkan, Cavaletti, Guido, Gutierrez-Gutierrez, Gerardo, Barroso, Fabio A., Visser, Leo H., Katzberg, Hans D., Dardiotis, Efthimios, Attarian, Shahram, van der Kooi, Anneke J., Eftimov, Filip, Wirtz, Paul W., Samijn, Johnny P. A., Gilhuis, H. Jacobus, Hadden, Robert D. M., Holt, James K. L., Sheikh, Kazim A., Karafiath, Summer, Vytopil, Michal, Antonini, Giovanni, Feasby, Thomas E., Faber, Catharina G., Gijsbers, Cees J., Busby, Mark, Roberts, Rhys C., Silvestri, Nicholas J., Fazio, Raffaella, van Dijk, Gert W., Garssen, Marcel P. J., Straathof, Chiara S. M., Gorson, Kenneth C., Jacobs, Bart C., Doets, Alex Y., Lingsma, Hester F., Walgaard, Christa, Islam, Badrul, Papri, Nowshin, Davidson, Amy, Kusunoki, Susumu, Dimachkie, Mazen M., Waheed, Waqar, Kolb, Noah, Islam, Zhahirul, Mohammad, Quazi Deen, Harbo, Thomas, Sindrup, Soren H., Chavada, Govindsinh, Willison, Hugh J., Casasnovas, Carlos, Bateman, Kathleen, Miller, James A. L., van den Berg, Bianca, Verboon, Christine, Roodbol, Joyce, Leonhard, Sonja E., Benedetti, Luana, Kuwabara, Satoshi, Van den Bergh, Peter, Monges, Soledad, Marfia, Girolama A., Shahrizaila, Nortina, Galassi, Giuliana, Pereon, Yann, Burmann, Jan, Kuitwaard, Krista, Kleyweg, Ruud P., Marchesoni, Cintia, Tous, Maria J. Sedano, Querol, Luis, Illa, Isabel, Wang, Yuzhong, Nobile-Orazio, Eduardo, Rinaldi, Simon, Schenone, Angelo, Pardo, Julio, Vermeij, Frederique H., Lehmann, Helmar C., Granit, Volkan, Cavaletti, Guido, Gutierrez-Gutierrez, Gerardo, Barroso, Fabio A., Visser, Leo H., Katzberg, Hans D., Dardiotis, Efthimios, Attarian, Shahram, van der Kooi, Anneke J., Eftimov, Filip, Wirtz, Paul W., Samijn, Johnny P. A., Gilhuis, H. Jacobus, Hadden, Robert D. M., Holt, James K. L., Sheikh, Kazim A., Karafiath, Summer, Vytopil, Michal, Antonini, Giovanni, Feasby, Thomas E., Faber, Catharina G., Gijsbers, Cees J., Busby, Mark, Roberts, Rhys C., Silvestri, Nicholas J., Fazio, Raffaella, van Dijk, Gert W., Garssen, Marcel P. J., Straathof, Chiara S. M., Gorson, Kenneth C., and Jacobs, Bart C.

Abstract

Background and Objectives The clinical course and outcome of the Guillain-Barre syndrome (GBS) are diverse and vary among regions. The modified Erasmus GBS Outcome Score (mEGOS), developed with data from Dutch patients, is a clinical model that predicts the risk of walking inability in patients with GBS. The study objective was to validate the mEGOS in the International GBS Outcome Study (IGOS) cohort and to improve its performance and region specificity. Methods We used prospective data from the first 1,500 patients included in IGOS, aged >= 6 years and unable to walk independently. We evaluated whether the mEGOS at entry and week 1 could predict the inability to walk unaided at 4 and 26 weeks in the full cohort and in regional subgroups, using 2 measures for model performance: (1) discrimination: area under the receiver operating characteristic curve (AUC) and (2) calibration: observed vs predicted probability of being unable to walk independently. To improve the model predictions, we recalibrated the model containing the overall mEGOS score, without changing the individual predictive factors. Finally, we assessed the predictive ability of the individual factors. Results For validation of mEGOS at entry, 809 patients were eligible (Europe/North America [n = 677], Asia [n = 76], other [n = 56]), and 671 for validation of mEGOS at week 1 (Europe/North America [n = 563], Asia [n = 65], other [n = 43]). AUC values were >0.7 in all regional subgroups. In the Europe/North America subgroup, observed outcomes were worse than predicted; in Asia, observed outcomes were better than predicted. Recalibration improved model accuracy and enabled the development of a region-specific version for Europe/North America (mEGOS-Eu/NA). Similar to the original mEGOS, severe limb weakness and higher age were the predominant predictors of poor outcome in the IGOS cohort. Discussion mEGOS is a validated tool to predict the inability to walk unaided at 4 and 26 weeks in patients with GBS, a

Published
2022

39. Predicting Outcome in Guillain-Barré Syndrome: International Validation of the Modified Erasmus GBS Outcome Score

Author

Doets, A, Lingsma, H, Walgaard, C, Islam, B, Papri, N, Davidson, A, Yamagishi, Y, Kusunoki, S, Dimachkie, M, Waheed, W, Kolb, N, Islam, Z, Mohammad, Q, Harbo, T, Sindrup, S, Chavada, G, Willison, H, Casasnovas, C, Bateman, K, Miller, J, van den Berg, B, Verboon, C, Roodbol, J, Leonhard, S, Benedetti, L, Kuwabara, S, Van den Bergh, P, Monges, S, Marfia, G, Shahrizaila, N, Galassi, G, Péréon, Y, Bürmann, J, Kuitwaard, K, Kleyweg, R, Marchesoni, C, Sedano Tous, M, Querol, L, Illa, I, Wang, Y, Nobile-Orazio, E, Rinaldi, S, Schenone, A, Pardo, J, Vermeij, F, Lehmann, H, Granit, V, Cavaletti, G, Gutiérrez-Gutiérrez, G, Barroso, F, Visser, L, Katzberg, H, Dardiotis, E, Attarian, S, van der Kooi, A, Eftimov, F, Wirtz, P, Samijn, J, Gilhuis, H, Hadden, R, Holt, J, Sheikh, K, Karafiath, S, Vytopil, M, Antonini, G, Feasby, T, Faber, C, Gijsbers, C, Busby, M, Roberts, R, Silvestri, N, Fazio, R, van Dijk, G, Garssen, M, Straathof, C, Gorson, K, Jacobs, B, Doets, Alex Y, Lingsma, Hester F, Walgaard, Christa, Islam, Badrul, Papri, Nowshin, Davidson, Amy, Yamagishi, Yuko, Kusunoki, Susumu, Dimachkie, Mazen M, Waheed, Waqar, Kolb, Noah, Islam, Zhahirul, Mohammad, Quazi Deen, Harbo, Thomas, Sindrup, Soren H, Chavada, Govindsinh, Willison, Hugh J, Casasnovas, Carlos, Bateman, Kathleen, Miller, James A L, van den Berg, Bianca, Verboon, Christine, Roodbol, Joyce, Leonhard, Sonja E, Benedetti, Luana, Kuwabara, Satoshi, Van den Bergh, Peter, Monges, Soledad, Marfia, Girolama A, Shahrizaila, Nortina, Galassi, Giuliana, Péréon, Yann, Bürmann, Jan, Kuitwaard, Krista, Kleyweg, Ruud P, Marchesoni, Cintia, Sedano Tous, María J, Querol, Luis, Illa, Isabel, Wang, Yuzhong, Nobile-Orazio, Eduardo, Rinaldi, Simon, Schenone, Angelo, Pardo, Julio, Vermeij, Frederique H, Lehmann, Helmar C, Granit, Volkan, Cavaletti, Guido, Gutiérrez-Gutiérrez, Gerardo, Barroso, Fabio A, Visser, Leo H, Katzberg, Hans D, Dardiotis, Efthimios, Attarian, Shahram, van der Kooi, Anneke J, Eftimov, Filip, Wirtz, Paul W, Samijn, Johnny P A, Gilhuis, H Jacobus, Hadden, Robert D M, Holt, James K L, Sheikh, Kazim A, Karafiath, Summer, Vytopil, Michal, Antonini, Giovanni, Feasby, Thomas E, Faber, Catharina G, Gijsbers, Cees J, Busby, Mark, Roberts, Rhys C, Silvestri, Nicholas J, Fazio, Raffaella, van Dijk, Gert W, Garssen, Marcel P J, Straathof, Chiara S M, Gorson, Kenneth C, Jacobs, Bart C, Doets, A, Lingsma, H, Walgaard, C, Islam, B, Papri, N, Davidson, A, Yamagishi, Y, Kusunoki, S, Dimachkie, M, Waheed, W, Kolb, N, Islam, Z, Mohammad, Q, Harbo, T, Sindrup, S, Chavada, G, Willison, H, Casasnovas, C, Bateman, K, Miller, J, van den Berg, B, Verboon, C, Roodbol, J, Leonhard, S, Benedetti, L, Kuwabara, S, Van den Bergh, P, Monges, S, Marfia, G, Shahrizaila, N, Galassi, G, Péréon, Y, Bürmann, J, Kuitwaard, K, Kleyweg, R, Marchesoni, C, Sedano Tous, M, Querol, L, Illa, I, Wang, Y, Nobile-Orazio, E, Rinaldi, S, Schenone, A, Pardo, J, Vermeij, F, Lehmann, H, Granit, V, Cavaletti, G, Gutiérrez-Gutiérrez, G, Barroso, F, Visser, L, Katzberg, H, Dardiotis, E, Attarian, S, van der Kooi, A, Eftimov, F, Wirtz, P, Samijn, J, Gilhuis, H, Hadden, R, Holt, J, Sheikh, K, Karafiath, S, Vytopil, M, Antonini, G, Feasby, T, Faber, C, Gijsbers, C, Busby, M, Roberts, R, Silvestri, N, Fazio, R, van Dijk, G, Garssen, M, Straathof, C, Gorson, K, Jacobs, B, Doets, Alex Y, Lingsma, Hester F, Walgaard, Christa, Islam, Badrul, Papri, Nowshin, Davidson, Amy, Yamagishi, Yuko, Kusunoki, Susumu, Dimachkie, Mazen M, Waheed, Waqar, Kolb, Noah, Islam, Zhahirul, Mohammad, Quazi Deen, Harbo, Thomas, Sindrup, Soren H, Chavada, Govindsinh, Willison, Hugh J, Casasnovas, Carlos, Bateman, Kathleen, Miller, James A L, van den Berg, Bianca, Verboon, Christine, Roodbol, Joyce, Leonhard, Sonja E, Benedetti, Luana, Kuwabara, Satoshi, Van den Bergh, Peter, Monges, Soledad, Marfia, Girolama A, Shahrizaila, Nortina, Galassi, Giuliana, Péréon, Yann, Bürmann, Jan, Kuitwaard, Krista, Kleyweg, Ruud P, Marchesoni, Cintia, Sedano Tous, María J, Querol, Luis, Illa, Isabel, Wang, Yuzhong, Nobile-Orazio, Eduardo, Rinaldi, Simon, Schenone, Angelo, Pardo, Julio, Vermeij, Frederique H, Lehmann, Helmar C, Granit, Volkan, Cavaletti, Guido, Gutiérrez-Gutiérrez, Gerardo, Barroso, Fabio A, Visser, Leo H, Katzberg, Hans D, Dardiotis, Efthimios, Attarian, Shahram, van der Kooi, Anneke J, Eftimov, Filip, Wirtz, Paul W, Samijn, Johnny P A, Gilhuis, H Jacobus, Hadden, Robert D M, Holt, James K L, Sheikh, Kazim A, Karafiath, Summer, Vytopil, Michal, Antonini, Giovanni, Feasby, Thomas E, Faber, Catharina G, Gijsbers, Cees J, Busby, Mark, Roberts, Rhys C, Silvestri, Nicholas J, Fazio, Raffaella, van Dijk, Gert W, Garssen, Marcel P J, Straathof, Chiara S M, Gorson, Kenneth C, and Jacobs, Bart C

Abstract

Background and objectives: The clinical course and outcome of the Guillain-Barré syndrome (GBS) are diverse and vary among regions. The modified Erasmus GBS Outcome Score (mEGOS), developed with data from Dutch patients, is a clinical model that predicts the risk of walking inability in patients with GBS. The study objective was to validate the mEGOS in the International GBS Outcome Study (IGOS) cohort and to improve its performance and region specificity. Methods: We used prospective data from the first 1,500 patients included in IGOS, aged ≥6 years and unable to walk independently. We evaluated whether the mEGOS at entry and week 1 could predict the inability to walk unaided at 4 and 26 weeks in the full cohort and in regional subgroups, using 2 measures for model performance: (1) discrimination: area under the receiver operating characteristic curve (AUC) and (2) calibration: observed vs predicted probability of being unable to walk independently. To improve the model predictions, we recalibrated the model containing the overall mEGOS score, without changing the individual predictive factors. Finally, we assessed the predictive ability of the individual factors. Results: For validation of mEGOS at entry, 809 patients were eligible (Europe/North America [n = 677], Asia [n = 76], other [n = 56]), and 671 for validation of mEGOS at week 1 (Europe/North America [n = 563], Asia [n = 65], other [n = 43]). AUC values were >0.7 in all regional subgroups. In the Europe/North America subgroup, observed outcomes were worse than predicted; in Asia, observed outcomes were better than predicted. Recalibration improved model accuracy and enabled the development of a region-specific version for Europe/North America (mEGOS-Eu/NA). Similar to the original mEGOS, severe limb weakness and higher age were the predominant predictors of poor outcome in the IGOS cohort. Discussion: mEGOS is a validated tool to predict the inability to walk unaided at 4 and 26 weeks in patients with

Published
2022

40. The legacy of ZikaPLAN:a transnational research consortium addressing Zika

Author

Wilder-Smith, Annelies, Brickley, Elizabeth B., Ximenes, Ricardo Arraes de Alencar, Miranda-Filho, Demócrito de Barros, Turchi Martelli, Celina Maria, Solomon, Tom, Jacobs, Bart C., Pardo, Carlos A., Osorio, Lyda, Parra, Beatriz, Lant, Suzannah, Willison, Hugh J., Leonhard, Sonja, Turtle, Lance, Ferreira, Maria Lúcia Brito, de Oliveira Franca, Rafael Freitas, Lambrechts, Louis, Neyts, Johan, Kaptein, Suzanne, Peeling, Rosanna, Boeras, Deborah, Logan, James, Dolk, Helen, Orioli, Ieda M., Neumayr, Andreas, Lang, Trudie, Baker, Bonny, Massad, Eduardo, Preet, Raman, Wilder-Smith, Annelies, Brickley, Elizabeth B., Ximenes, Ricardo Arraes de Alencar, Miranda-Filho, Demócrito de Barros, Turchi Martelli, Celina Maria, Solomon, Tom, Jacobs, Bart C., Pardo, Carlos A., Osorio, Lyda, Parra, Beatriz, Lant, Suzannah, Willison, Hugh J., Leonhard, Sonja, Turtle, Lance, Ferreira, Maria Lúcia Brito, de Oliveira Franca, Rafael Freitas, Lambrechts, Louis, Neyts, Johan, Kaptein, Suzanne, Peeling, Rosanna, Boeras, Deborah, Logan, James, Dolk, Helen, Orioli, Ieda M., Neumayr, Andreas, Lang, Trudie, Baker, Bonny, Massad, Eduardo, and Preet, Raman

Abstract

Global health research partnerships with institutions from high-income countries and low- and middle-income countries are one of the European Commission's flagship programmes. Here, we report on the ZikaPLAN research consortium funded by the European Commission with the primary goal of addressing the urgent knowledge gaps related to the Zika epidemic and the secondary goal of building up research capacity and establishing a Latin American-European research network for emerging vector-borne diseases. Five years of collaborative research effort have led to a better understanding of the full clinical spectrum of congenital Zika syndrome in children and the neurological complications of Zika virus infections in adults and helped explore the origins and trajectory of Zika virus transmission. Individual-level data from ZikaPLAN`s cohort studies were shared for joint analyses as part of the Zika Brazilian Cohorts Consortium, the European Commission-funded Zika Cohorts Vertical Transmission Study Group, and the World Health Organization-led Zika Virus Individual Participant Data Consortium. Furthermore, the legacy of ZikaPLAN includes new tools for birth defect surveillance and a Latin American birth defect surveillance network, an enhanced Guillain-Barre Syndrome research collaboration, a de-centralized evaluation platform for diagnostic assays, a global vector control hub, and the REDe network with freely available training resources to enhance global research capacity in vector-borne diseases.

Published
2022

47. The endogenous calpain inhibitor calpastatin attenuates axon degeneration in murine Guillain‐Barré syndrome.

Author

McGonigal, Rhona, Cunningham, Madeleine E., Smyth, Duncan, Chou, Michael, Barrie, Jennifer A., Wilkie, Andrew, Campbell, Clare, Saatman, Kathryn E., Lunn, Michael, and Willison, Hugh J.

Subjects
IN vivo studies, NERVE tissue proteins, ANIMAL experimentation, PROTEOLYTIC enzymes, MONOCLONAL antibodies, GENE expression, GUILLAIN-Barre syndrome, RESEARCH funding, NEURODEGENERATION, MICE, PHRENIC nerve, CHEMICAL inhibitors
Abstract

Axon degeneration accounts for the poor clinical outcome in Guillain‐Barré syndrome (GBS), yet no treatments target this key pathogenic stage. Animal models demonstrate anti‐ganglioside antibodies (AGAb) induce axolemmal complement pore formation through which calcium flux activates the intra‐axonal calcium‐dependent proteases, calpains. We previously showed protection of axonal components using soluble calpain inhibitors in ex vivo GBS mouse models, and herein, we assess the potential of axonally‐restricted calpain inhibition as a neuroprotective therapy operating in vivo. Using transgenic mice that over‐express the endogenous human calpain inhibitor calpastatin (hCAST) neuronally, we assessed distal motor nerve integrity in our established GBS models. We induced immune‐mediated injury with monoclonal AGAb plus a source of human complement. The calpain substrates neurofilament and AnkyrinG, nerve structural proteins, were assessed by immunolabelling and in the case of neurofilament, by single‐molecule arrays (Simoa). As the distal intramuscular portion of the phrenic nerve is prominently targeted in our in vivo model, respiratory function was assessed by whole‐body plethysmography as the functional output in the acute and extended models. hCAST expression protects distal nerve structural integrity both ex and in vivo, as shown by attenuation of neurofilament breakdown by immunolabelling and Simoa. In an extended in vivo model, while mice still initially undergo respiratory distress owing to acute conduction failure, the recovery phase was accelerated by hCAST expression. Axonal calpain inhibition can protect the axonal integrity of the nerve in an in vivo GBS paradigm and hasten recovery. These studies reinforce the strong justification for developing further animal and human clinical studies using exogenous calpain inhibitors. [ABSTRACT FROM AUTHOR]

Published
2023
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48. The role of gangliosides in the organisation of the node of Ranvier examined in glycosyltransferase transgenic mice

Author

McGonigal, Rhona and Willison, Hugh J.

Subjects
Nervous system, Genetically modified mouse, Histology, Mice, Transgenic, Ligands, chemistry.chemical_compound, Mice, Gangliosides, Glycosyltransferase, medicine, Transferase, Animals, Receptor, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Autoantibodies, Node of Ranvier, biology, Glycosyltransferases, Cell Biology, Axons, N-Acetylneuraminic Acid, Sialyltransferases, Sialic acid, Cell biology, medicine.anatomical_structure, chemistry, biology.protein, Anatomy, Glycolipids, NODAL, Developmental Biology
Abstract

Gangliosides are a family of sialic acid containing glycosphingolipids highly enriched in plasma membranes of the vertebrate nervous system. They are functionally diverse in modulating nervous system integrity, notably at the node of Ranvier, and also act as receptors for many ligands including toxins and autoantibodies. They are synthesised in a stepwise manner by groups of glycosyl- and sialyltransferases in a developmentally and tissue regulated manner. In this review, we summarise and discuss data derived from transgenic mice with different transferase deficiencies that have been used to determine the role of glycolipids in the organisation of the node of Ranvier. Understanding their role at this specialised functional site is crucial to determining differential pathophysiology following directed genetic or autoimmune injury to peripheral nerve nodal or paranodal domains, and revealing the downstream consequences of axo-glial disruption.

Published
2021

49. Guía basada en la evidencia. Diagnóstico y manejo del síndrome de Guillain-Barré en diez pasos = Evidence based guidelines. Diagnosis and management of Guillain-Barré syndrome in ten steps

Author

Leonhard, Sonja E., Mandarakas, Melissa R., de Assis Aquino Gondim, Francisco, Bateman, Kathleen, Brito Ferreira, Maria L., Cornblath, David R., Van Doorn, Pieter A., Dourado, Mario E., Hughes, Richard A.C., Islam, Badrul, Kusunoki, Susumu, Pardo, Carlos A., Reisin, Ricardo, Sejvar, James J., Shahrizaila, Nortina, Soares, Cristiane, Umapathi, Thirugnanam, Wang, Yuzhong, Yiu, Eppie M., Willison, Hugh J., and Jacobs, Bart C.

Abstract

Guillain-Barré syndrome (GBS) is a rare, but potentially fatal, immune-mediated disease of the peripheral nerves and nerve roots that is usually triggered by infections. The incidence of GBS can therefore increase during outbreaks of infectious diseases, as was seen during the Zika virus epidemics in 2013 in French Polynesia and in 2015 in Latin America. Diagnosis and management of GBS can be complicated as its clinical presentation and disease course are heterogeneous, and no international clinical guidelines are currently available. To support clinicians, especially in the context of an outbreak, we have developed a globally applicable guideline for the diagnosis and management of GBS. The guideline is based on current literature and expert consensus, and has a ten-step structure to facilitate its use in clinical practice. We first provide an introduction to the diagnostic criteria, clinical variants and differential diagnoses of GBS. The ten steps then cover early recognition and diagnosis of GBS, admission to the intensive care unit, treatment indication and selection, monitoring and treatment of disease progression, prediction of clinical course and outcome, and management of complications and sequelae.

Published
2021

50. Oligodendrocytes are susceptible to Zika virus infection in a mouse model of perinatal exposure: implications for CNS complications

Author

Schultz, Verena, Barrie, Jennifer A., Donald, Claire L., Crawford, Colin L., Mullin, Margaret, Anderson, Thomas J., Solomon, Tom, Barnett, Susan C., Linington, Christopher, Kohl, Alain, Willison, Hugh J., and Edgar, Julia M.

Abstract

Some children with proven intrauterine Zika virus (ZIKV) infection who were born asymptomatic subsequently manifested neurodevelopmental delays, pointing to impairment of development perinatally and postnatally. To model this, we infected postnatal day (P) 5–6 (equivalent to the perinatal period in humans) susceptible mice with a mammalian cell‐propagated ZIKV clinical isolate from the Brazilian outbreak in 2015. All infected mice appeared normal up to 4 days post‐intraperitoneal inoculation (dpi), but rapidly developed severe clinical signs at 5–6 dpi. All nervous tissue examined at 5/6 dpi appeared grossly normal. However, anti‐ZIKV positive cells were observed in the optic nerve, brain, and spinal cord; predominantly in white matter. Co‐labeling with cell type specific markers demonstrated oligodendrocytes and astrocytes support productive infection. Rarely, ZIKV positive neurons were observed. In spinal cord white matter, which we examined in detail, apoptotic cells were evident; the density of oligodendrocytes was significantly reduced; and there was localized microglial reactivity including expression of the NLRP3 inflammasome. Together, our observations demonstrate that a clinically relevant ZIKV isolate can directly impact oligodendrocytes. As primary oligodendrocyte cell death can lead later to secondary autoimmune demyelination, our observations may help explain neurodevelopmental delays in infants appearing asymptomatic at birth and commend lifetime surveillance.

Published
2021

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