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Current treatment NMO

Michael Absoud, Peter Brex, Olga Ciccarelli, Onyinye Diribe, Gavin Giovannoni, Jennifer Hellier, Rosemary Howe, Rachel Holland, Joanna Kelly, Paul McCrone, Caroline Murphy, Jackie Palace, Andrew Pickles, Michael Pike, Neil Robertson, Anu Jacob, Ming Lim
BACKGROUND: Transverse myelitis (TM) is an immune-mediated disorder of the spinal cord that affects adults and children and that causes motor, sensory and autonomic dysfunction. There is a prolonged recovery phase, which may continue for many years. Neuromyelitis optica (NMO) is an uncommon relapsing inflammatory central nervous system condition in which TM can be the first presenting symptom. As TM and NMO affect many patients in the prime of their working life, the disorder can impose a significant demand on health resources...
May 2017: Health Technology Assessment: HTA
Lev Stimmer, Claire-Maëlle Fovet, Ché Serguera
Human idiopathic inflammatory demyelinating diseases (IIDD) are a heterogeneous group of autoimmune inflammatory and demyelinating disorders of the central nervous system (CNS). These include multiple sclerosis (MS), the most common chronic IIDD, but also rarer disorders such as acute disseminated encephalomyelitis (ADEM) and neuromyelitis optica (NMO). Great efforts have been made to understand the pathophysiology of MS, leading to the development of a few effective treatments. Nonetheless, IIDD still require a better understanding of the causes and underlying mechanisms to implement more effective therapies and diagnostic methods...
January 1, 2017: Veterinary Pathology
Velina S Chavarro, Maureen A Mealy, Alexandra Simpson, Anna Lacheta, Florence Pache, Klemens Ruprecht, Stefan M Gold, Friedemann Paul, Alexander Ulrich Brandt, Michael Levy
OBJECTIVE: To investigate depression frequency, severity, current treatment, and interactions with somatic symptoms among patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: In this dual-center observational study, we included 71 patients diagnosed with NMOSD according to the International Panel for NMO Diagnosis 2015 criteria. The Beck Depression Inventory (BDI) was classified into severe, moderate, or minimal/no depressive state category. We used the Fatigue Severity Scale to evaluate fatigue...
December 2016: Neurology® Neuroimmunology & Neuroinflammation
Larry Steinman, Amit Bar-Or, Jacinta M Behne, Daniel Benitez-Ribas, Peter S Chin, Michael Clare-Salzler, Donald Healey, James I Kim, David M Kranz, Andreas Lutterotti, Roland Martin, Sven Schippling, Pablo Villoslada, Cheng-Hong Wei, Howard L Weiner, Scott S Zamvil, Michael R Yeaman, Terry J Smith
Neuromyelitis optica (NMO) and spectrum disorder (NMO/SD) represent a vexing process and its clinical variants appear to have at their pathogenic core the loss of immune tolerance to the aquaporin-4 water channel protein. This process results in a characteristic pattern of astrocyte dysfunction, loss, and demyelination that predominantly affects the spinal cord and optic nerves. Although several empirical therapies are currently used in the treatment of NMO/SD, none has been proven effective in prospective, adequately powered, randomized trials...
October 2016: Neurology® Neuroimmunology & Neuroinflammation
Silvia Tenembaum, Tanuja Chitnis, Ichiro Nakashima, Nicolas Collongues, Andrew McKeon, Michael Levy, Kevin Rostasy
Neuromyelitis optica (NMO) is a severe autoimmune disease of the CNS characterized by recurrent inflammatory events primarily involving the optic nerves and spinal cord. NMO is infrequent in children, but early recognition is important to start adequate treatment. In this article, we review the evolving diagnostic criteria of NMO and provide an update on the clinical and neuroimaging spectrum of the disorder in pediatric patients, including current knowledge on immunopathogenesis and treatment recommendations for children with NMO...
August 30, 2016: Neurology
Michael Absoud, Benjamin M Greenberg, Ming Lim, Tim Lotze, Terrence Thomas, Kumaran Deiva
Pediatric acute transverse myelitis (ATM) is an immune-mediated CNS disorder and contributes to 20% of children experiencing a first acquired demyelinating syndrome (ADS). ATM must be differentiated from other presentations of myelopathy and may be the first presentation of relapsing ADS such as neuromyelitis optica (NMO) or multiple sclerosis (MS). The tenets of the diagnostic criteria for ATM established by the Transverse Myelitis Consortium Working Group can generally be applied in children; however, a clear sensory level may not be evident in some...
August 30, 2016: Neurology
Adi Vaknin-Dembinsky, Hanna Charbit, Livnat Brill, Oded Abramsky, Devorah Gur-Wahnon, Iddo Z Ben-Dov, Iris Lavon
BACKGROUND: Neuromyelitis optica (NMO) is a chronic autoimmune disease of the central nervous system (CNS). The main immunological feature of the disease is the presence of autoantibodies to Aquaporin 4 (AQP4+), identified in about 82 % of cases. Currently, there are no reliable biomarkers for monitoring treatment response in patients with NMO. In an effort to identify biomarkers, we analyzed microRNAs (miRNAs) in the blood of rituximab-treated NMO patients before and after therapy. METHODS: Total RNA extracted from whole blood of nine rituximab-responsive NMO patients before and 6 months following treatment was subjected to small RNAseq analysis...
July 8, 2016: Journal of Neuroinflammation
Ilana Katz Sand
PURPOSE OF REVIEW: This article provides a practical approach for providers caring for patients with neuromyelitis optica (NMO) spectrum disorders. Clinical and imaging features, diagnostic criteria, treatment of acute exacerbations, chronic preventive therapy, and symptom management in NMO spectrum disorders are discussed. RECENT FINDINGS: The rapid pace of research in NMO spectrum disorders has led to many recent advances. A broader understanding of the clinical spectrum of the disease as well as improvements in anti-aquaporin-4 antibody assays have led to recent revision of the diagnostic criteria...
August 2016: Continuum: Lifelong Learning in Neurology
Xiaoming Yao, Tao Su, A S Verkman
Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system that can produce marked neurological deficit. Current NMO therapies include immunosuppressants, plasma exchange and B-cell depletion. Here, we evaluated 14 potential remyelinating drugs emerging from prior small molecule screens done to identify drugs for repurposing in multiple sclerosis and other demyelinating neurological diseases. Compounds were initially evaluated in oligodendrocyte precursor cell (OPC) and cerebellar slice cultures, and then in a mouse model of NMO produced by intracerebral injection of anti-AQP4 autoantibody (AQP4-IgG) and human complement characterized by demyelination with minimal axonal damage...
April 26, 2016: Acta Neuropathologica Communications
Bogdan F Gh Popescu, Claudia F Lucchinetti
While multiple sclerosis (MS) is often referred to as an autoimmune inflammatory demyelinating disease, neuromyelitis optica (NMO) is currently the only proven and well-characterized autoimmune disease affecting the glial cells. The target antigen is the water channel aquaporin-4 (AQP4), expressed on astrocytes, and antibodies against AQP4 (AQP4-IgG) are present in the serum of NMO patients. Clinical, serologic, cerebrospinal fluid, and neuroimaging criteria help differentiate NMO from other central nervous system inflammatory demyelinating disorders...
2016: Handbook of Clinical Neurology
Michalina Jasiak-Zatonska, Alicja Kalinowska-Lyszczarz, Slawomir Michalak, Wojciech Kozubski
Neuromyelitis optica (NMO) is an autoimmune, demyelinating disorder of the central nervous system (CNS) with typical clinical manifestations of optic neuritis and acute transverse myelitis attacks. Previously believed to be a variant of multiple sclerosis (MS), it is now considered an independent disorder which needs to be differentiated from MS. The discovery of autoantibodies against aquaporin-4 (AQP4-IgGs) changed our understanding of NMO immunopathogenesis and revolutionized the diagnostic process. AQP4-IgG is currently regarded as a specific biomarker of NMO and NMO spectrum disorders (NMOsd) and a key factor in its pathogenesis...
March 2, 2016: International Journal of Molecular Sciences
Maureen A Mealy, Kyong Shin, Gareth John, Michael Levy
OBJECTIVES: Neuromyelitis optica (NMO) is a relapsing autoimmune disease targeting the spinal cord and optic nerve leading to paralysis and blindness. Current treatment for acute NMO attacks is immunosuppression with high-dose corticosteroids and/or plasmapheresis. Preclinical animal studies suggest that bevacizumab might be beneficial in limiting the extent of inflammation during a NMO relapse by reducing the disruption of the blood-brain barrier. METHODS: We carried out an open-label phase 1b safety and proof-of-concept trial in 10 participants with NMO immunoglobulin G seropositive NMO, NMO spectrum disease and those at high risk for developing NMO/NMO spectrum disease who presented with an acute attack of transverse myelitis, optic neuritis or brainstem inflammation...
November 1, 2015: Clinical & Experimental Neuroimmunology
Bruce A C Cree
Currently, there are no approved treatments for NMO. All therapeutic studies in NMO have been either small, retrospective case series or uncontrolled prospective studies. Such studies are susceptible to inherent biases. As a consequence, conclusions regarding efficacy and safety from these studies may be erroneous. The optimal method for assessing therapeutic efficacy is the prospective, controlled trial with random treatment assignment that has the potential to control for multiple sources of bias. There is a significant unmet need for well-designed clinical trials in NMO...
November 2015: Multiple Sclerosis and related Disorders
P S Rommer, T Dörner, K Freivogel, J Haas, B C Kieseier, T Kümpfel, F Paul, F Proft, H Schulze-Koops, E Schmidt, H Wiendl, U Ziemann, U K Zettl
INTRODUCTION: Multiple sclerosis (MS) is an immune-mediated disease. Over the last decades therapeutic options have broadened tremendously. Nevertheless, various therapeutic agents, e.g., rituximab, are currently used in the treatment of MS off label. Disease or health registries are useful methods to collect information about off-label treatments. The German registry for autoimmune disease (GRAID) is a multicenter, retrospective, non-interventional database of patients with various autoimmune diseases...
March 2016: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
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
Elena Sherman, May H Han
Neuromyelitis optica and neuromyelitis optica spectrum disorder (NMO/NMOSD) is a rare but clinically aggressive demyelinating disease of the central nervous system (CNS) caused by antibodies against water channel protein aquaporin 4 (AQP4) in the astrocytic foot processes. Patients typically present with optic neuritis (ON) or longitudinally extensive transverse myelitis (LETM). The majority of patients with NMOSD show good response to treatment with steroids and plasmapheresis in the acute setting; however, 90 % of patients will eventually have clinical relapses and accrue permanent disability...
November 2015: Current Treatment Options in Neurology
Ivana Vodopivec, Marcelo Matiello, Sashank Prasad
PURPOSE OF REVIEW: Neuromyelitis optica (NMO) is an antibody-mediated inflammatory disease of the central nervous system with a predilection for the optic nerves, spinal cord and certain brain regions. It has a distinct pathogenesis relating to aquaporin-4 autoimmunity and complement-mediated injury. This knowledge has translated into targeted efforts to develop novel, disease-specific treatments. In this review, we discuss evidence supporting the use of currently available treatments for acute exacerbations and for long-term disease modification...
November 2015: Current Opinion in Ophthalmology
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
T O Simaniv, A A Vorob'eva, N V Smirnova, N A Zigangirova, M N Zakharova
Identification of aquaporin-4 antibodies in neuromyelitis optica (NMO) is highly important to provide early diagnosis for starting pathogenetic treatment, and for differential diagnosis in neuromyelitis optica spectrum disorders (NMO-SD). In this paper, we review current pathogenetic and clinical aspects of NMO and NMO NMO-SD. We present our data on the identification of aquaporin-4 antibodies in CNS disorders. Aquaporin-4 antibodies were detected in 86.36% of patients with neuromyelitis optica, in 12.5% of patients with partial syndromes and in 100% of patients with systemic lupus erythematosus with longitudinally extensive transverse myelitis or optic neuritis...
2015: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
Brian G Weinshenker, Gerard Barron, Jacinta M Behne, Jeffery L Bennett, Peter S Chin, Bruce A C Cree, Jerome de Seze, Armando Flor, Kazuo Fujihara, Benjamin Greenberg, Sayumi Higashi, William Holt, Omar Khan, Volker Knappertz, Michael Levy, Angela T Melia, Jacqueline Palace, Terry J Smith, Maria Pia Sormani, Katja Van Herle, Susan VanMeter, Pablo Villoslada, Marc K Walton, Warren Wasiewski, Dean M Wingerchuk, Michael R Yeaman
Current management of neuromyelitis optica (NMO) is noncurative and only partially effective. Immunosuppressive or immunomodulatory agents are the mainstays of maintenance treatment. Safer, better-tolerated, and proven effective treatments are needed. The perceived rarity of NMO has impeded clinical trials for this disease. However, a diagnostic biomarker and recognition of a wider spectrum of NMO presentations has expanded the patient population from which study candidates might be recruited. Emerging insights into the pathogenesis of NMO have provided rationale for exploring new therapeutic targets...
April 28, 2015: Neurology
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