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Jun-Ichi Kira
Some disease-modifying drugs for multiple sclerosis, which mainly act on T cells, are ineffective for neuromyelitis optica spectrum disorder and induce unexpected relapses. These include interferon beta, glatiramer acetate, fingolimod, natalizumab, and alemtuzumab. The cases reported here suggest that dimethyl fumarate, which reduces the number of Th1 and Th17 cells and induces IL-4-producing Th2 cells, is also unsuitable for neuromyelitis optica spectrum disorder, irrespective of anti-aquaporin 4 IgG serostatus...
April 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
Brian G Weinshenker, Dean M Wingerchuk
The understanding of neuromyelitis optica spectrum disorder (NMOSD) has evolved substantially since its initial description over a century ago. The discovery in 2004 of a pathogenic autoantibody biomarker targeting aquaporin 4 IgG revolutionized diagnosis and therapeutic development. Although NMOSD resembles multiple sclerosis (MS), differences were identified and articulated in the late 1990s. New diagnostic criteria incorporating the biomarker as well as better understanding of the clinical and radiologic features of NMOSD now permit accurate diagnosis and differentiation from MS...
April 2017: Mayo Clinic Proceedings
Yeseul Kim, Gayoung Kim, Byung Soo Kong, Ji Eun Lee, Yu Mi Oh, Jae Won Hyun, Su Hyun Kim, AeRan Joung, Byoung Joon Kim, Kyungho Choi, Ho Jin Kim
BACKGROUND AND PURPOSE: The detection of aquaporin 4-IgG (AQP4-IgG) is now a critical diagnostic criterion for neuromyelitis optica spectrum disorder (NMOSD). To evaluate the serostatus of NMOSD patients based on the 2015 new diagnostic criteria using a new in-house cell-based assay (CBA). METHODS: We generated a stable cell line using internal ribosome entry site-containing bicistronic vectors, which allow the simultaneous expression of two proteins (AQP4 and green fluorescent protein) separately from the same RNA transcript...
April 2017: Journal of Clinical Neurology
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
Yanlu Huang, Yuge Wang, Yifan Zhou, Qiao Huang, Xiaobo Sun, Chen Chen, Ling Fang, Youming Long, Hui Yang, Honghao Wang, Caixia Li, Zhengqi Lu, Xueqiang Hu, Allan G Kermode, Wei Qiu
OBJECTIVE: This study aimed to assess the effect of pregnancy on the course of neuromyelitis optica spectrum disorder (NMOSD), and the effect of this disease on pregnancy outcomes. METHODS: Consecutive patients with NMOSD were recruited between September 2015 and April 2016 at an outpatient clinic from four referral institutes in South China. Demographic, clinical, and pregnancy data were retrieved by questionnaires to analyze the association between NMOSD and pregnancy, as well as the potential risk factors for relapse...
January 15, 2017: Journal of the Neurological Sciences
Kerstin Soelberg, Stine R Larsen, Marlene T Moerch, Mads Thomassen, Klaus Brusgaard, Friedemannn Paul, Terry J Smith, Christian Godballe, Jakob Grauslund, Soeren T Lillevang, Nasrin Asgari
No abstract text is available yet for this article.
August 2016: Neurology® Neuroimmunology & Neuroinflammation
Eoin P Flanagan
Autoimmune myelopathies are a heterogeneous group of immune-mediated spinal cord disorders with a broad differential diagnosis. They encompass myelopathies with an immune attack on the spinal cord (e.g., aquaporin-4-IgG (AQP4-IgG) seropositive neuromyelitis optica (NMO) and its spectrum disorders (NMOSD)), myelopathies occurring with systemic autoimmune disorders (which may also be due to coexisting NMO/NMOSD), paraneoplastic autoimmune myelopathies, postinfectious autoimmune myelopathies (e.g., acute disseminated encephalomyelitis), and myelopathies thought to be immune-related (e...
2016: Handbook of Clinical Neurology
Kavitha Kothur, Louise Wienholt, Esther M Tantsis, John Earl, Sushil Bandodkar, Kristina Prelog, Fiona Tea, Sudarshini Ramanathan, Fabienne Brilot, Russell C Dale
BACKGROUND: Myelin oligodendrocyte glycoprotein antibody (MOG Ab) associated demyelination represents a subgroup of autoimmune demyelination that is separate from multiple sclerosis and aquaporin 4 IgG-positive NMO, and can have a relapsing course. Unlike NMO and MS, there is a paucity of literature on immunopathology and CSF cytokine/chemokines in MOG Ab associated demyelination. AIM: To study the differences in immunopathogenesis based on cytokine/chemokine profile in MOG Ab-positive (POS) and -negative (NEG) groups...
2016: PloS One
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
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
Maciej Juryńczyk, Brian Weinshenker, Gulsen Akman-Demir, Nasrin Asgari, David Barnes, Mike Boggild, Abhijit Chaudhuri, Marie D'hooghe, Nikos Evangelou, Ruth Geraldes, Zsolt Illes, Anu Jacob, Ho Jin Kim, Ingo Kleiter, Michael Levy, Romain Marignier, Christopher McGuigan, Katy Murray, Ichiro Nakashima, Lekha Pandit, Friedemann Paul, Sean Pittock, Krzysztof Selmaj, Jérôme de Sèze, Aksel Siva, Radu Tanasescu, Sandra Vukusic, Dean Wingerchuk, Damian Wren, Isabel Leite, Jacqueline Palace
Distinguishing aquaporin-4 IgG(AQP4-IgG)-negative neuromyelitis optica spectrum disorders (NMOSD) from opticospinal predominant multiple sclerosis (MS) is a clinical challenge with important treatment implications. The objective of the study was to examine whether expert clinicians diagnose and treat NMO/MS overlapping patients in a similar way. 12 AQP4-IgG-negative patients were selected to cover the range of clinical scenarios encountered in an NMO clinic. 27 NMO and MS experts reviewed their clinical vignettes, including relevant imaging and laboratory tests...
January 2016: Journal of Neurology
Eda Derle, H Nalan Güneş, Bahadır Konuşkan, Aslı Tuncer-Kurne
Neuromyelitis optica (NMO) is a rare and severe inflammatory disease of the central nervous system (CNS), which constitutes up to 5% of pediatric aquired demyelinating diseases. The optic nerves and the spinal cord are the most affected sites. The discovery of an autoantibody called NMO-IgG, which targets aquaporin-4, the main water channel in the CNS, gave a new direction to understanding the underlying immunologic mechanisms. This specific biomarker also helps to distinguish the disease from other demyelinating disorders...
November 2014: Turkish Journal of Pediatrics
Nasrin Asgari, Carsten Tue Berg, Marlene Thorsen Mørch, Reza Khorooshi, Trevor Owens
To clarify the significance of immunoglobulin G autoantibody specific for the astrocyte water channel aquaporin-4 in cerebrospinal fluid, aquaporin-4-immunoglobulin G from a neuromyelitis optica patient was administered intrathecally to naïve mice, and the distribution and pathogenic impact was evaluated. A distinct distribution pattern of aquaporin-4-immunoglobulin G deposition was observed in the subarachnoid and subpial spaces where vessels penetrate the brain parenchyma, via a paravascular route with intraparenchymal perivascular deposition...
August 2015: Annals of Clinical and Translational Neurology
S Jarius, O Aktas, B Wildemann
Neuromyelitis optica (NMO; also termed Devic's disease) is a severely disabling autoimmune disorder of the central nervous system (CNS), which predominantly affects the optic nerves and spinal cord. In up to 80% of cases, NMO is associated with antibodies to aquaporin-4 (AQP4-IgG), the most abundant water channel in the CNS. AQP4-IgG have been demonstrated to be directly pathogenic. Gamma-aminobutyric acid A receptor (GABAAR) agonists are frequently used in patients with NMO, e.g., for symptomatic treatment of spasticity or epilepsy or for non-NMO-related indications such as treatment of insomnia...
November 2015: Medical Hypotheses
Melanie Ramberger, Gabriel Bsteh, Kathrin Schanda, Romana Höftberger, Kevin Rostásy, Matthias Baumann, Fahmy Aboulenein-Djamshidian, Andreas Lutterotti, Florian Deisenhammer, Thomas Berger, Markus Reindl
OBJECTIVES: To analyze the frequency of NMDA receptor (NMDAR) antibodies in patients with various inflammatory demyelinating diseases of the CNS and to determine their clinical correlates. METHODS: Retrospective case-control study from 2005 to 2014 with the detection of serum IgG antibodies to NMDAR, aquaporin-4, and myelin oligodendrocyte glycoprotein by recombinant live cell-based immunofluorescence assays. Fifty-one patients with acute disseminated encephalomyelitis, 41 with neuromyelitis optica spectrum disorders, 34 with clinically isolated syndrome, and 89 with multiple sclerosis (MS) were included...
October 2015: Neurology® Neuroimmunology & Neuroinflammation
Hiroto Nakano, Kenichi Sakajiri, Eishun Nitta, Atsushi Nagata, Toshiyuki Takahashi
We describe a case of 20-year-old woman with visual impairment in her left eye. Her left visual acuity was 0.07 and an ophthalmoscopic examination demonstrated bilateral intermediate uveitis (IU). A neurological examination on admission revealed lower nasal quadrantanopsia in her left eye and an exaggerated right patellar tendon reflex. A T2-weighted MRI showed multiple high-intensity lesions in the bilateral periventricular region, corpus callosum, medulla. A short T1 inversion recovery MRI also showed a swollen left retrobulbar optic nerve and posterior thoracic cord lesion at Th 9 level...
2015: Rinshō Shinkeigaku, Clinical Neurology
Esther Melamed, Michael Levy, Patrick J Waters, Douglas Kazutoshi Sato, Jeffrey L Bennett, Gareth R John, Douglas C Hooper, Albert Saiz, Amit Bar-Or, Ho Jin Kim, Lakha Pandit, Maria Isabel Leite, Nasrin Asgari, Najib Kissani, Rogier Hintzen, Romain Marignier, Sven Jarius, John Marcelletti, Terry J Smith, Michael R Yeaman, May H Han, Orhan Aktas, Metha Apiwattanakul, Brenda Banwell, Denis Bichuetti, Simon Broadley, Philippe Cabre, Tanuja Chitnis, Jerome De Seze, Kazuo Fujihara, Benjamin Greenberg, Kerstin Hellwig, Raffaele Iorio, Sven Jarius, Eric Klawiter, Ingo Kleiter, Marco Lana-Peixoto, Nakashima, Kevin O'Connor, Jacqueline Palace, Friedman Paul, Naraporn Prayoonwiwat, Klemens Ruprecht, Olaf Stuve, Thomas Tedder, Silvia Tenembaum, Juan P Garrahan, Buenos Aires, Katja van Herle, Danielle van Pelt, Pablo Villoslada, Emmanuelle Waubant, Brian Weinshenker, Dean Wingerchuk, Jens Würfel, Scott Zamvil
Neuromyelitis optica (NMO) (and NMO spectrum disorder) is an autoimmune inflammatory disease of the CNS primarily affecting spinal cord and optic nerves. Reliable and sensitive biomarkers for onset, relapse, and progression in NMO are urgently needed because of the heterogeneous clinical presentation, severity of neurologic disability following relapses, and variability of therapeutic response. Detecting aquaporin-4 (AQP4) antibodies (AQP4-IgG or NMO-IgG) in serum supports the diagnosis of seropositive NMO...
August 2015: Neurology® Neuroimmunology & Neuroinflammation
Anastasia Zekeridou, Vanda A Lennon
Neuromyelitis optica (NMO) and a related spectrum of inflammatory CNS disorders are unified by detection of a serum autoantibody specific for the aquaporin-4 (AQP4) water channel, which is abundant in astrocytic foot processes. The classic clinical manifestations of NMO are optic neuritis and longitudinally extensive transverse myelitis. Newly recognized manifestations of AQP4 autoimmunity include lesions of circumventricular organs and skeletal muscle. NMO is commonly relapsing, is frequently accompanied by other autoimmune disorders, and sometimes occurs in a paraneoplastic context...
August 2015: Neurology® Neuroimmunology & Neuroinflammation
Minshu Li, Yaping Yan
Neuromyelitis optica (NMO) is a recurrent inflammatory disease that predominantly attacks the opticnerves and spinal cord. NMO-IgG, the specific autoantibody present in the vast majority of NMO patients, targets the astrocytic water channel protein aquaporin 4 (AQP4), and differentiates NMO from multiple sclerosis. The growing clinical and research interest in NMO makes it urgent to produce an animal model of NMO. The pathogenic effect of anti-AQP4 antibodies derived from the serum of patients paves the way to generating an experimental model based on the anti-AQP4-mediated astrocyte damage...
December 2015: Neuroscience Bulletin
Sean J Pittock, Claudia F Lucchinetti
The discovery of AQP4-IgG (a pathogenic antibody that targets the astrocytic water channel aquaporin-4), as the first sensitive and specific biomarker for any inflammatory central nervous system demyelinating disease (IDD), has shifted emphasis from the oligodendrocyte and myelin to the astrocyte as a central immunopathogenic player. Neuromyelitis optica (NMO) spectrum disorders (SDs) represent an evolving spectrum of IDDs extending beyond the optic nerves and spinal cord to include the brain (especially in children) and, rarely, muscle...
February 2016: Annals of the New York Academy of Sciences
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