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Jenny Linnoila, Sean J Pittock
Autoimmune neurology is a rapidly evolving new subspecialty driven by the discovery of novel neural- (neuronal- or glial-) specific autoantibodies and their target antigens. The neurologic manifestations affecting the central nervous system include encephalitis, dementia, epilepsy, and movement and sleep disorders. Laboratory testing is now available for most of these neural-specific autoantibodies, which serve as diagnostic markers, in some instances directing the physician toward specific cancer types (e...
August 2016: Seminars in Neurology
Boyan Fang, Andrew McKeon, Shannon R Hinson, Thomas J Kryzer, Sean J Pittock, Allen J Aksamit, Vanda A Lennon
Importance: A novel astrocytic autoantibody has been identified as a biomarker of a relapsing autoimmune meningoencephalomyelitis that is immunotherapy responsive. Seropositivity distinguishes autoimmune glial fibrillary acidic protein (GFAP) meningoencephalomyelitis from disorders commonly considered in the differential diagnosis. Objective: To describe a novel IgG autoantibody found in serum or cerebrospinal fluid that is specific for a cytosolic intermediate filament protein of astrocytes...
September 12, 2016: JAMA Neurology
Rajat Lahoria, Sean J Pittock, Avi Gadoth, JaNean K Engelstad, Vanda A Lennon, Christopher J Klein
INTRODUCTION: Voltage-gated Kv1 potassium channel-complex (VGKC) autoantibodies subtyped for leucine-rich-glioma-inactivated-1 (LGI1), contactin-associated-protein-like-2 (CASPR2), and Kv-IgGs have a spectrum of neurological presentations. Painful polyneuropathy is seen in some patients, but nerve pathology descriptions are lacking. METHODS: Clinicopathologic features were studied in subtyped VGKC-autoantibody seropositive patients who had undergone nerve biopsies...
August 11, 2016: Muscle & Nerve
Dae Hee Park, Lynn Wang, Paula Pittock, Gilles Lajoie, Shawn Narain Whitehead
Neurons within different brain regions have varying levels of vulnerability to external stress and respond differently to injury. A potential reason to explain this may lie within a key lipid class of the cell's plasma membrane called gangliosides. These glycosphingolipid species have been shown to play various roles in the maintenance of neuronal viability. The purpose of this study is to use electrospray ionization mass spectrometry (ESI-MS) and immunohistochemistry to evaluate the temporal expression profiles of gangliosides during the course of neurodegeneration in rat primary cortical neurons exposed to glutamate toxicity...
August 2, 2016: Analytical Chemistry
Masoud Majed, James P Fryer, Andrew McKeon, Vanda A Lennon, Sean J Pittock
OBJECTIVE: To define, using assays of optimized sensitivity and specificity, the most informative specimen type for aquaporin-4 immunoglobulin G (AQP4-IgG) detection. METHODS: Results were reviewed from longitudinal service testing for AQP4-IgG among specimens submitted to the Mayo Clinic Neuroimmunology Laboratory from 101,065 individual patients. Paired samples of serum/CSF were tested from 616 patients, using M1-AQP4-transfected cell-based assays (both fixed AQP4-CBA Euroimmun kit [commercial CBA] and live in-house flow cytometry [FACS])...
June 2016: Neurology® Neuroimmunology & Neuroinflammation
Sean J Pittock, Angela Vincent
No abstract text is available yet for this article.
2016: Handbook of Clinical Neurology
Melody Y Hu, Panos Stathopoulos, Kevin C O'connor, Sean J Pittock, Richard J Nowak
Randomized controlled treatment trials of autoimmune neurologic disorders are generally lacking and data pertaining to treatment are mostly derived from expert opinion, large case series, and anecdotal reports. The treatment of autoimmune neurologic disorders comprises oncologic therapy (where appropriate) and immunotherapy. In this chapter, we first describe the standard acute and chronic immunotherapies and provide a practical overview of their use in the clinic (mechanisms of action, dosing, monitoring, and side effects)...
2016: Handbook of Clinical Neurology
Shannon R Hinson, Vanda A Lennon, Sean J Pittock
Neuromyelitis optica (NMO) spectrum disorders (SD) represent an evolving group of central nervous system (CNS)-inflammatory autoimmune demyelinating diseases unified by a pathogenic autoantibody specific for the aquaporin-4 (AQP4) water channel. It was historically misdiagnosed as multiple sclerosis (MS), which lacks a distinguishing biomarker. The discovery of AQP4-IgG moved the focus of CNS demyelinating disease research from emphasis on the oligodendrocyte and myelin to the astrocyte. NMO is recognized today as a relapsing disease, extending beyond the optic nerves and spinal cord to include brain (especially in children) and skeletal muscle...
2016: Handbook of Clinical Neurology
Sean J Pittock, Jacqueline Palace
Autoimmune neurology is a rapidly emerging new subspecialty that encompasses the diagnosis and treatment of neurologic disorders with an autoimmune (paraneoplastic or noncancer-associated) basis. The last decade has seen a dramatic rise in the discovery of neural-specific autoantibodies and their target antigens. Laboratory testing, on a service basis, is now available for most of these neural-specific autoantibodies and they serve as diagnostic markers, in some instances directing the physician toward specific cancer types (e...
2016: Handbook of Clinical Neurology
Sean J Pittock, Angela Vincent
Considering the diversity and numbers of targets expressed on the estimated 500 billion glia and slightly less numerous but more diverse neurons, if any channel, receptor or protein on such a cell can be the target of the immune system, we need only imagine the possibilities. As those before us looked to the heavens and ultimately walked on the moon, we need to recognize the potential implications of autoimmune neurology - a new subspecialty in neurology that has truly launched! Its importance cannot be overstated as many of the disorders now recognized as autoimmune are treatable and reversible, representing a shift from the traditional view held by many in the lay and medical community that neurologists diagnose but don't treat! In this introductory chapter we provide a brief over-view of how the field developed, tabulate the authors and contents of the individual topics covered in each chapter, and describe some of the on-going challenges of the field...
2016: Handbook of Clinical Neurology
Emeline Hassenforder, Marcela Brugnach, Beth Cullen, Nils Ferrand, Olivier Barreteau, Katherine Anne Daniell, Jamie Pittock
Many participatory processes fail to generate social change and collaborative outcomes. This failure can partly be explained by how divergent stakeholders' frames are handled. This paper builds on the framing and participation literature to explain how facilitators can manage frame diversity and foster collaborative outcomes. It suggests two pragmatic steps: identifying frames and managing frames. The two steps are applied to a participatory process for natural resource management in Fogera, Ethiopia. Effectiveness of facilitators' strategies to manage frame diversity in the Fogera case is discussed...
July 15, 2016: Journal of Environmental Management
Eoin P Flanagan, Philippe Cabre, Brian G Weinshenker, Jennifer St Sauver, Debra J Jacobson, Masoud Majed, Vanda A Lennon, Claudia F Lucchinetti, Andrew McKeon, Marcelo Matiello, Nilifur Kale, Dean M Wingerchuk, Jay Mandrekar, Jessica A Sagen, James P Fryer, Angala Borders Robinson, Sean J Pittock
Objective Neuromyelitis optica and its spectrum disorders (NMOSD) are inflammatory demyelinating diseases (IDD) with a specific biomarker, aquaporin-4-IgG. Prior NMO/NMOSD epidemiological studies are limited by lack of aquaporin-4-IgG seroprevalence assessment, absence of population-based USA studies and under-representation of blacks. To overcome these limitations, we sought to compare NMO/NMOSD seroepidemiology across two ethnically divergent populations. Methods We performed a population-based comparative study of the incidence (2003-2011) and prevalence (on December 31, 2011) of NMO/NMOSD and aquaporin-4-IgG seroincidence and seroprevalence (sera collected in 80-84% of IDD) among patients with IDD diagnosis in Olmsted County, USA (82% white [Caucasian]) and Martinique (90% black [Afro-Caribbean])...
February 17, 2016: Annals of Neurology
A Sebastian Lopez-Chiriboga, Lars Komorowski, Tania Kümpfel, Christian Probst, Shannon R Hinson, Sean J Pittock, Andrew McKeon
OBJECTIVE: To describe retrospectively the clinical associations of immunoglobulin G (IgG) targeting metabotropic glutamate receptor 1 (mGluR1-IgG). METHODS: Specimens of 9 patients evaluated on a service basis in the Mayo Clinic Neuroimmunology Laboratory by tissue-based immunofluorescence assay (IFA) yielded a robust, synaptic immunostaining pattern consistent with mGluR1-IgG (serum, 9; CSF, 2 available). Transfected HEK293 cell-based assay (CBA) confirmed mGluR1 specificity in all 11 specimens...
March 15, 2016: Neurology
Sean J Pittock
No abstract text is available yet for this article.
March 2016: Nature Reviews. Neurology
Weiping Sun, Miljan Kuljanin, Paula Pittock, Bin Ma, Kaizhong Zhang, Gilles A Lajoie
Mass spectrometry has become a widely used analytical technique for proteomics study because of its high throughput and sensitivity. Among those applications, a specific one is to characterize glycan structure. Glycosylation is a frequently occurred post-translational modification of proteins which is relevant to humans' health. Therefore, it is significant to develop effective computational methods to automate the identification of glycan structures from mass spectral data. In our research, we mathematically formulated the glycan de novo sequencing problem and proposed a heuristic algorithm for glycan de novo sequencing from HCD MS/MS spectra of N-linked glycopeptides...
March 2016: IEEE Transactions on Nanobioscience
Nicholas L Zalewski, Vanda A Lennon, Daniel H Lachance, Christopher J Klein, Sean J Pittock, Andrew Mckeon
INTRODUCTION: Voltage-gated calcium-channel autoimmunity (VGCC-P/Q and VGCC-N types) occurs beyond Lambert-Eaton syndrome and lung cancer. METHODS: We reviewed records for 236 Mayo Clinic patients with VGCC antibodies found in evaluation for paraneoplastic neurological autoimmunity (generally without myasthenic syndromes). RESULTS: VGCC autoantibodies were detected in 3.4% of neurological patients, 1.7% of healthy controls, and 4% of neurologically asymptomatic lung cancer controls...
August 2016: Muscle & Nerve
Eoin P Flanagan, Timothy J Kaufmann, Karl N Krecke, Allen J Aksamit, Sean J Pittock, B Mark Keegan, Caterina Giannini, Brian G Weinshenker
OBJECTIVE: To compare longitudinally extensive myelitis in neuromyelitis optica spectrum disorders (NMOSD) and spinal cord sarcoidosis (SCS). METHODS: We identified adult patients evaluated between 1996 and 2015 with SCS or NMOSD whose first myelitis episode was accompanied by a spinal cord lesion spanning ≥3 vertebral segments. All NMOSD patients were positive for aquaporin-4-immunoglobulin G, and all sarcoidosis cases were pathologically confirmed. Clinical characteristics were evaluated...
March 2016: Annals of Neurology
Najwa Zebian, Alexandra Merkx-Jacques, Paula P Pittock, Sebastien Houle, Charles M Dozois, Gilles A Lajoie, Carole Creuzenet
Campylobacter jejuni is the leading cause of bacterial gastroenteritis. It relies on several virulence factors for host colonization, including glycosylated flagella. C. jejuni NCTC 11168 modifies its flagellins with pseudaminic acid derivatives. It is also presumed to modify these proteins with legionaminic acid, although no glycopeptide evidence was available at the onset of this study. The enzyme encoded by cj1319 can be used to make legionaminic acid in vitro, but the pathway for legionaminic acid synthesis partially inferred by knockout mutagenesis in Campylobacter coli VC167 excludes Cj1319...
April 2016: Glycobiology
Metha Apiwattanakul, Margherita Milone, Sean J Pittock, Thomas J Kryzer, James P Fryer, Orna O'toole, Andrew Mckeon, Vanda A Lennon
INTRODUCTION: Paraneoplastic autoantibody screening of 150,000 patient sera by tissue-based immunofluorescence incidentally revealed 170 with unsuspected signal recognition particle (SRP) immunoglobulin G (IgG), which is a recognized biomarker of autoimmune myopathy. Of the 77 patients with available information, 54 had myopathy. We describe the clinical/laboratory associations. METHODS: Distinctive cytoplasm-binding IgG (mouse tissue substrate) prompted western blot, enzyme-linked immunoassay, and immunoprecipitation analyses...
June 2016: Muscle & Nerve
David R Barnidge, Mindy C Kohlhagen, Sunny Zheng, Maria A V Willrich, Jerry A Katzmann, Sean J Pittock, David L Murray
Our group has previously shown that mass spectrometry can be used to detect and quantify monoclonal and polyclonal immunoglobulin light chains in serum and urine from patients with monoclonal gammopathies and polyclonal hypergammaglobinemia. Here we demonstrate the use of the methodology, also referred to as monoclonal immunoglobulin Rapid Accurate Mass Measurement\with (miRAMM), to detect oligoclonal immunoglobulins above the polyclonal background in cerebral spinal fluid (CSF) and serum. We compared the findings for 56 paired CSF and serum samples analyzed by IgG IEF and miRAMM...
November 15, 2015: Journal of Neuroimmunology
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