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https://www.readbyqxmd.com/read/30103974/distinction-between-anti-vgkc-complex-seropositive-patients-with-and-without-anti-lgi1-caspr2-antibodies
#1
Tianrong Yeo, Zhiyong Chen, Kok Pin Yong, Patricia Yut Wan Wong, Josiah Yui Huei Chai, Kevin Tan
BACKGROUND: To identify clinical and paraclinical differences between anti-voltage-gated potassium channel (VGKC)-complex seropositive patients with and without anti-leucine-rich glioma-inactivated protein 1 (LGI1)/contactin-associated protein-like 2 (CASPR2) antibodies (Abs). METHODS: We performed a retrospective analysis of 50 anti-VGKC-complex seropositive patients from January 2013 to September 2016, and tested them for anti-LGI1/CASPR2 Abs. Comparative analysis was performed between anti-LGI1/CASPR2 seropositive and 'double negative' patients...
August 15, 2018: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/30090985/morvan-s-syndrome-is-a-pathogen-behind-the-curtain
#2
Rohit Singh, Pritam Das, Upinder Kaur, Anamika Misra, Ashis Choudhury, Sukdev Manna, Rohit Gaude, Deepak Gautam, Indrajeet Singh Gambhir, Sankha Shubhra Chakrabarti
Morvan's syndrome is a rare syndrome of likely autoimmune etiology characterized by peripheral nerve hyperexcitability, dysautonomia, insomnia, and fluctuating delirium with prominent hallucinations. Since its first mention in 1890, less than 100 cases have been described in literature. The largest existing review includes details of 29 cases. This case series describes 4 cases (M = 4) of Morvan's syndrome which presented between May and November 2017 to a single tertiary care referral teaching hospital in north India...
August 9, 2018: Neurological Sciences
https://www.readbyqxmd.com/read/30076629/lgi1-and-caspr2-neurological-autoimmunity-in-children
#3
A Sebastian Lopez-Chiriboga, Christopher Klein, Anastasia Zekeridou, Andrew McKeon, Divanshu Dubey, Eoin P Flanagan, Vanda A Lennon, Jan-Mendelt Tillema, Elaine C Wirrell, Marc C Patterson, Avi Gadoth, J Gregory Aaen, J Nicholas Brenton, Jonathan D Bui, Amanda Moen, Catherine Otten, Amanda Piquet, Sean J Pittock
The clinical phenotype of leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) autoimmunity is well defined in adults. Data for children are limited (<10 cases). Among 13,319 pediatric patients serologically tested for autoimmune neurological disorders (2010-2017), 264 were seropositive for VGKC-complex-IgG (radioimmunoprecipitation). Only 13 (4.9%) were positive by transfected cell-binding assay for: LGI1-IgG (7), CASPR2-IgG (3) or both (3). This is significantly less than in adults...
August 3, 2018: Annals of Neurology
https://www.readbyqxmd.com/read/30028556/contactin-associated-protein-like-2-caspr2-a-protein-of-the-neurexin-family-involved-in-several-human-diseases
#4
REVIEW
Margaux Saint-Martin, Bastien Joubert, Véronique Pellier-Monnin, Olivier Pascual, Nelly Noraz, Jérôme Honnorat
CASPR2 (Contactin-associated protein-like 2) is a cell adhesion protein of the neurexin family. Proteins of this family have been shown to play a role in the development of the nervous system, in synaptic functions, and in neurological diseases. Over recent years, CASPR2 function has gained an increasing interest as demonstrated by the growing number of publications. Here, we gather published data to comprehensively review CASPR2 functions within the nervous system in relation to CASPR2-related diseases in humans...
July 20, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29954343/autoantibodies-against-neuronal-surface-proteins-in-spontaneous-subarachnoid-and-intracerebral-haemorrhage
#5
Harald Hegen, Raimund Helbok, Mario Kofler, Bettina Pfausler, Alois Schiefecker, Erich Schmutzhard, Ronny Beer
BACKGROUND: Brain autoimmunity has been reported in patients with preceding infection of the central nervous system by herpesviridae. It has been hypothesized that neuronal damage releasing antigens might trigger secondary immune response. The objective of the study was to investigate whether brain damage due to spontaneous subarachnoid haemorrhage (SAH) or intracerebral haemorrhage (ICH) induces reactivity against neuronal surface proteins. METHODS: Patients with spontaneous SAH and ICH, who had cerebrospinal fluid (CSF) and serum sampling within 2 weeks after disease onset (baseline) and afterwards at least 10 days later (follow-up), were included...
June 28, 2018: BMC Neurology
https://www.readbyqxmd.com/read/29951031/evaluation-of-clinical-and-paraclinical-findings-for-the-differential-diagnosis-of-autoimmune-and-infectious-encephalitis
#6
Judith N Wagner, Ognian Kalev, Michael Sonnberger, Ingomar Krehan, Tim J von Oertzen
Background: The differential diagnosis of autoimmune and infectious encephalitis is notoriously difficult. For this study, we compare the presenting clinical symptoms and paraclinical test results of autoimmune and infectious encephalitis patients. A clinical algorithm for the diagnosis of autoimmune encephalitis has recently been published. We test these Graus criteria on our cohort for diagnostic sensitivity and specificity within the first week of presentation. Methods: We included all patients seen at our department within a 10-year-period who were diagnosed with encephalitis...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29788256/distinct-hla-associations-of-lgi1-and-caspr2-antibody-diseases
#7
Sophie Binks, James Varley, Wanseon Lee, Mateusz Makuch, Katherine Elliott, Jeffrey M Gelfand, Saiju Jacob, M Isabel Leite, Paul Maddison, Mian Chen, Michael D Geschwind, Eleanor Grant, Arjune Sen, Patrick Waters, Mark McCormack, Gianpiero L Cavalleri, Martin Barnardo, Julian C Knight, Sarosh R Irani
The recent biochemical distinction between antibodies against leucine-rich, glioma-inactivated-1 (LGI1), contactin-associated protein-2 (CASPR2) and intracellular epitopes of voltage-gated potassium-channels (VGKCs) demands aetiological explanations. Given established associations between human leucocyte antigen (HLA) alleles and adverse drug reactions, and our clinical observation of frequent adverse drugs reactions in patients with LGI1 antibodies, we compared HLA alleles between healthy controls (n = 5553) and 111 Caucasian patients with VGKC-complex autoantibodies...
May 18, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29788201/genetic-variants-in-autism-related-cntnap2-impair-axonal-growth-of-cortical-neurons
#8
Giorgia Canali, Marta Garcia, Bruno Hivert, Delphine Pinatel, Aline Goullancourt, Ksenia Oguievetskaia, Margaux Saint-Martin, Jean-Antoine Girault, Catherine Faivre-Sarrailh, Laurence Goutebroze
The CNTNAP2 gene, coding for the cell adhesion glycoprotein Caspr2, is thought to be one of the major susceptibility genes for autism spectrum disorder (ASD). A large number of rare heterozygous missense CNTNAP2 variants have been identified in ASD patients. However, most of them are inherited from an unaffected parent, questioning their clinical significance. In the present study, we evaluate their impact on neurodevelopmental functions of Caspr2 in a heterozygous genetic background. Performing cortical neuron cultures from mouse embryos, we demonstrate that Caspr2 plays a dose-dependent role in axon growth in vitro...
June 1, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29774053/postherpes-simplex-encephalitis-a-case-series-of-viral-triggered-autoimmunity-synaptic-autoantibodies-and-response-to-therapy
#9
Harry Alexopoulos, Sofia Akrivou, Sotiria Mastroyanni, Maria Antonopoulou, Argirios Dinopoulos, Melpo Giorgi, Kostas Konstantinou, Evangelos Kouremenos, Maria Lariou, Dimitrios Naoumis, Efterpi Pavlidou, Evaggelos Pavlou, Konstantinos Voudris, Panayotis Vlachoyiannopoulos, Marinos C Dalakas
Background: Recent evidence suggests that patients with herpes simplex virus (HSV) encephalitis may relapse because of autoimmunity against the N-methyl-D-aspartate receptor (NMDAR). We present a case series of post-HSV relapsing encephalopathy associated with antibodies to central nervous system (CNS) synaptic antigens. Patient/Methods: Sera and cerebrospinal fluid (CSF) from five patients with HSV encephalitis who relapsed after antiviral therapy were tested for anti-NMDAR, gamma-aminobutyric acid b receptor (GABAbR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), Leucine-rich, glioma inactivated 1 (LGI1), anti -contactin-associated protein-like 2 (CASPR2) and dipeptidyl-peptidase-like protein-6 (DDPX) antibodies using cell-based assays...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29761119/antibodies-against-cell-adhesion-molecules-and-neural-structures-in-paraneoplastic-neuropathies
#10
Ana M Siles, Eugenia Martínez-Hernández, Josefa Araque, Jordi Diaz-Manera, Ricard Rojas-Garcia, Eduard Gallardo, Isabel Illa, Francesc Graus, Luis Querol
Objective: Paraneoplastic neurological syndromes (PNS) are rare neurological disorders in which ectopic expression of neural antigens by a tumor results in an autoimmune attack against the nervous system. Onconeural antibodies not only guide PNS diagnosis but may also help detecting underlying malignancies. Our project aims to uncover new potential antibodies in paraneoplastic neuropathies (PN). Methods: Thirty-four patients fulfilling diagnostic criteria of possible ( n = 9; 26...
May 2018: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/29720798/mercury-toxicity-following-unauthorized-siddha-medicine-intake-a-mimicker-of-acquired-neuromyotonia-report-of-32-cases
#11
G Gnanashanmugam, R Balakrishnan, S P Somasundaram, N Parimalam, P Rajmohan, M B Pranesh
Context: Mercury is used extensively in the preparation of Siddha medicines, after purification. In this study, we present 32 patients of mercury toxicity following unauthorized Siddha medicine intake who mimicked neuromyotonia clinically. We analyzed the clinical features of these patients, the role of autoimmunity in etiopathology, and compared it with acquired neuromyotonia. Subjects and Methods: This is a retrospective study to analyze inpatients in a tertiary care center, admitted with mercury toxicity following Siddha medicine intake from August 2012 to October 2016...
January 2018: Annals of Indian Academy of Neurology
https://www.readbyqxmd.com/read/29610228/video-neuroimages-paraneoplastic-spinal-myoclonus-associated-with-caspr2-antibodies
#12
Harrison Hines, Nick M Murray, Sarah Ahmad, Safwan Jaradeh, Carl A Gold
No abstract text is available yet for this article.
April 3, 2018: Neurology
https://www.readbyqxmd.com/read/29561731/paraneoplastic-movement-disorders
#13
Karolina Popławska-Domaszewicz, Jolanta Florczak-Wyspiańska, Wojciech Kozubski, Sławomir Michalak
Paraneoplastic movement disorders are rare, autoimmune-mediated, nonmetastatic complications of malignant neoplasms. Common paraneoplastic movement disorders include paraneoplastic chorea, dystonia, cerebellar degeneration, different types of encephalitis, opsoclonus-myoclonus syndrome, stiff person syndrome, and neuromyotonia. Syndromes usually develop before tumor diagnosis, have subacute onset, and are associated with serum or cerebrospinal fluid antibodies. Two types of antibodies can be distinguished: antibodies against nuclear and cytoplasmic neuronal antigens (anti-Hu, anti-Ri, anti-Yo, anti-Ma, anti-CV2/CRMP5, anti-Gephrin, and anti-GABATRAP) and antibodies recently identified against cell surface and synaptic proteins (anti-NMDAR, anti-LGI1, and anti-Caspr2)...
March 21, 2018: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/29470963/autoantibodies-hurt-transfer-of-patient-derived-caspr2-antibodies-induces-neuropathic-pain-in-mice
#14
Matthew A Hunt, Diana S M Nascimento, Alex Bersellini Farinotti, Camilla I Svensson
In this issue of Neuron, Dawes et al. (2018) show that CASPR2 antibodies (Abs) isolated from patients bind specifically to primary afferent cell bodies and induce neuropathic pain in mice. Consequent decreased expression of Kv1 channels and their aberrant localization along myelinated axons explain the observed hyperexcitability and pain.
February 21, 2018: Neuron
https://www.readbyqxmd.com/read/29429934/immune-or-genetic-mediated-disruption-of-caspr2-causes-pain-hypersensitivity-due-to-enhanced-primary-afferent-excitability
#15
John M Dawes, Greg A Weir, Steven J Middleton, Ryan Patel, Kim I Chisholm, Philippa Pettingill, Liam J Peck, Joseph Sheridan, Akila Shakir, Leslie Jacobson, Maria Gutierrez-Mecinas, Jorge Galino, Jan Walcher, Johannes Kühnemund, Hannah Kuehn, Maria D Sanna, Bethan Lang, Alex J Clark, Andreas C Themistocleous, Noboru Iwagaki, Steven J West, Karolina Werynska, Liam Carroll, Teodora Trendafilova, David A Menassa, Maria Pia Giannoccaro, Ester Coutinho, Ilaria Cervellini, Damini Tewari, Camilla Buckley, M Isabel Leite, Hendrik Wildner, Hanns Ulrich Zeilhofer, Elior Peles, Andrew J Todd, Stephen B McMahon, Anthony H Dickenson, Gary R Lewin, Angela Vincent, David L Bennett
Human autoantibodies to contactin-associated protein-like 2 (CASPR2) are often associated with neuropathic pain, and CASPR2 mutations have been linked to autism spectrum disorders, in which sensory dysfunction is increasingly recognized. Human CASPR2 autoantibodies, when injected into mice, were peripherally restricted and resulted in mechanical pain-related hypersensitivity in the absence of neural injury. We therefore investigated the mechanism by which CASPR2 modulates nociceptive function. Mice lacking CASPR2 (Cntnap2-/- ) demonstrated enhanced pain-related hypersensitivity to noxious mechanical stimuli, heat, and algogens...
February 21, 2018: Neuron
https://www.readbyqxmd.com/read/29332416/-autoimmune-encephalitis-possibilities-in-the-laboratory-investigation
#16
Katalin Böröcz, Zsófia Hayden, Viktória Mészáros, Zsuzsanna Csizmadia, Kornélia Farkas, Zoltán Kellermayer, Péter Balogh, Ferenc Nagy, Tímea Berki
INTRODUCTION: The role of autoimmune responses against central nervous system (CNS) antigens in encephalitis presenting with non-classified neurologic or psychiatric symptoms has been appreciated in the past decade. Paraneoplastic limbic encephalitis has a poor prognosis and is most commonly associated with lung, ovarium, and testicular neoplasms, leading to immune reactions against intracellular antigens (anti-Hu/ANNA1, anti-Ri/ANNA2, anti-CV2/CRMP5 and anti-Ma2/Ta). In contrast, the recently described autoimmune encephalitis subtypes present with a broad spectrum of symptoms, respond to autoimmune therapies well and usually associate with autoantibodies against neuronal cell surface receptors (NMDAR, GABAB R, AMPAR) or synaptic proteins (LGI1, CASPR2)...
January 2018: Orvosi Hetilap
https://www.readbyqxmd.com/read/29300891/loss-of-cntnap2-causes-axonal-excitability-deficits-developmental-delay-in-cortical-myelination-and-abnormal-stereotyped-motor-behavior
#17
Ricardo Scott, Alberto Sánchez-Aguilera, Kim van Elst, Lynette Lim, Nathalie Dehorter, Sung Eun Bae, Giorgia Bartolini, Elior Peles, Martien J H Kas, Hilgo Bruining, Oscar Marín
Contactin-associated protein-like 2 (Caspr2) is found at the nodes of Ranvier and has been associated with physiological properties of white matter conductivity. Genetic variation in CNTNAP2, the gene encoding Caspr2, has been linked to several neurodevelopmental conditions, yet pathophysiological effects of CNTNAP2 mutations on axonal physiology and brain myelination are unknown. Here, we have investigated mouse mutants for Cntnap2 and found profound deficiencies in the clustering of Kv1-family potassium channels in the juxtaparanodes of brain myelinated axons...
December 28, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29244234/mechanisms-of-caspr2-antibodies-in-autoimmune-encephalitis-and-neuromyotonia
#18
Kristina R Patterson, Josep Dalmau, Eric Lancaster
OBJECTIVE: To determine the pathogenic mechanisms of autoantibodies to the cell adhesion molecule Caspr2 in acquired neuromyotonia and autoimmune encephalitis. METHODS: Caspr2-positive samples were confirmed using a cell-based assay, and their IgG subtypes were determined by enzyme-linked immunosorbent assay and cell-based assay. A solid phase binding assay quantified the binding of Caspr2 to contactin-2 in the presence of Caspr2 autoantibodies. Living cultures of primary rat hippocampal neurons were incubated with Caspr2-positive or control sera, and the distribution of Caspr2-positive immunofluorescent puncta and total surface Caspr2 was quantified...
January 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29097081/paraneoplastic-autoimmune-movement-disorders
#19
REVIEW
Thien Thien Lim
PURPOSE OF REVIEW: To provide an overview of paraneoplastic autoimmune disorders presenting with various movement disorders. RECENT FINDINGS: The spectrum of paraneoplastic autoimmune disorders has been expanding with the discovery of new antibodies against cell surface and intracellular antigens. Many of these paraneoplastic autoimmune disorders manifest as a form of movement disorder. With the discovery of new neuronal antibodies, an increasing number of idiopathic or neurodegenerative movement disorders are now being reclassified as immune-mediated movement disorders...
November 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/29090003/structure-and-function-of-the-contactin-associated-protein-family-in-myelinated-axons-and-their-relationship-with-nerve-diseases
#20
REVIEW
Yan Zou, Wei-Feng Zhang, Hai-Ying Liu, Xia Li, Xing Zhang, Xiao-Fang Ma, Yang Sun, Shi-Yi Jiang, Quan-Hong Ma, De-En Xu
The contactin-associated protein (Caspr) family participates in nerve excitation and conduction, and neurotransmitter release in myelinated axons. We analyzed the structures and functions of the Caspr family-CNTNAP1 (Caspr1), CNTNAP2 (Caspr2), CNTNAP3 (Caspr3), CNTNAP4 (Caspr4) and CNTNAP5 (Caspr5), Caspr1-5 is not only involved in the formation of myelinated axons, but also participates in maintaining the stability of adjacent connections. Caspr1 participates in the formation, differentiation, and proliferation of neurons and astrocytes, and in motor control and cognitive function...
September 2017: Neural Regeneration Research
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