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Nasrin Asgari, Eoin P Flanagan, Kazuo Fujihara, Ho Jin Kim, Hanne P Skejoe, Jens Wuerfel, Hiroshi Kuroda, Su Hyun Kim, Elisabeth Maillart, Romain Marignier, Sean J Pittock, Friedemann Paul, Brian G Weinshenker
OBJECTIVE: To describe leptomeningeal blood-barrier impairment reflected by MRI gadolinium-enhanced lesions in patients with aquaporin-4 immunoglobulin G (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD). METHODS: A retrospective case series of 11 AQP4-IgG-positive NMOSD patients with leptomeningeal enhancement (LME) were collected from 5 centers. External neuroradiologists, blinded to the clinical details, evaluated MRIs. RESULTS: LME was demonstrated on postcontrast T1-weighted and fluid-attenuated inversion recovery images as a sign of leptomeningeal blood-barrier disruption and transient leakage of contrast agent into the subarachnoid space in 11 patients, 6 in the brain and 6 in the spinal cord...
July 2017: Neurology® Neuroimmunology & Neuroinflammation
E P Flanagan, S J Pittock
Most spinal cord injury is seen with trauma. Nontraumatic spinal cord emergencies are discussed in this chapter. These myelopathies are rare but potentially devastating neurologic disorders. In some situations prior comorbidity (e.g., advanced cancer) provides a clue, but in others (e.g., autoimmune myelopathies) it may come with little warning. Neurologic examination helps distinguish spinal cord emergencies from peripheral nervous system emergencies (e.g., Guillain-Barré), although some features overlap...
2017: Handbook of Clinical Neurology
Yong Guo, Stephen D Weigand, Bogdan F Popescu, Vanda A Lennon, Joseph E Parisi, Sean J Pittock, Natalie E Parks, Stacey L Clardy, Charles L Howe, Claudia F Lucchinetti
Pathogenic autoantibodies associated with neuromyelitis optica (NMO) induce disease by targeting aquaporin-4 (AQP4) water channels enriched on astrocytic endfeet at blood-brain interfaces. AQP4 is also expressed at cerebrospinal fluid (CSF)-brain interfaces, such as the pial glia limitans and the ependyma and at the choroid plexus blood-CSF barrier. However, little is known regarding pathology at these sites in NMO. Therefore, we evaluated AQP4 expression, microglial reactivity, and complement deposition at pial and ependymal surfaces and in the fourth ventricle choroid plexus in 23 autopsy cases with clinically and/or pathologically confirmed NMO or NMO spectrum disorder...
April 2017: Acta Neuropathologica
Eoin P Flanagan, Shannon R Hinson, Vanda A Lennon, Boyan Fang, Allen J Aksamit, P Pearse Morris, Eati Basal, Josephe A Honorat, Nora B Alfugham, Jenny J Linnoila, Brian G Weinshenker, Sean J Pittock, Andrew McKeon
OBJECTIVE: A novel autoimmune central nervous system (CNS) disorder with glial fibrillary acidic protein (GFAP)-IgG as biomarker was recently characterized. Here, 102 patients with GFAP-IgG positivity are described. METHODS: The 102 included patients had: (1) serum, cerebrospinal fluid (CSF), or both that yielded a characteristic astrocytic pattern of mouse tissue immunostaining; (2) confirmation of IgG reactive with specific GFAP isoforms (α, ɛ, or κ) by cell-based assays; and (3) clinical data available...
February 2017: Annals of Neurology
Divyanshu Dubey, Sean J Pittock, Karl N Krecke, Eoin P Flanagan
No abstract text is available yet for this article.
March 1, 2017: JAMA Neurology
Avi Gadoth, Thomas J Kryzer, Jim Fryer, Andrew McKeon, Vanda A Lennon, Sean J Pittock
OBJECTIVE: To report the identification of microtubule-associated protein (MAP) 1B as the antigen of the previously described Purkinje cell cytoplasmic antibody type 2 (PCA-2) antibody, its frequency, and clinical, oncological, and serological associations. METHODS: Archival serum or cerebrospinal fluid (CSF) specimens were available from 96 of 118 consecutive PCA-2-IgG-seropositive patients identified during 1993-2016. The autoantigen, defined in mouse brain lysate by Western blot and mass spectrometry, was confirmed by dual immunohistochemical staining using commercial antibodies...
February 2017: Annals of Neurology
Nicholas L Zalewski, Padraig P Morris, Brian G Weinshenker, Claudia F Lucchinetti, Yong Guo, Sean J Pittock, Karl N Krecke, Timothy J Kaufmann, Dean M Wingerchuk, Neeraj Kumar, Eoin P Flanagan
OBJECTIVE: We assessed the frequency and characteristics of ring-enhancing spinal cord lesions in neuromyelitis optica spectrum disorder (NMOSD) myelitis and myelitis of other cause. METHODS: We reviewed spinal cord MRIs for ring-enhancing lesions from 284 aquaporin-4 (AQP4)-IgG seropositive patients at Mayo Clinic from 1996 to 2014. Inclusion criteria were as follows: (1) AQP4-IgG seropositivity, (2) myelitis attack and (3) MRI spinal cord demonstrating ring-enhancement...
December 2, 2016: Journal of Neurology, Neurosurgery, and Psychiatry
Nora Alfugham, Matthew Roforth, Lars Komorowski, Anthonina Ott, Wolfgang Meyer, Christian Probst, Vanda A Lennon, Sean J Pittock, Andrew McKeon
No abstract text is available yet for this article.
December 2016: Neurology® Neuroimmunology & Neuroinflammation
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...
November 1, 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-proteinlike 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...
April 2017: 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
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