International consensus diagnostic criteria for neuromyelitis optica spectrum disorders
Mayo Clinic1, University of Pennsylvania2, Anschutz Medical Campus3, Sir Charles Gairdner Hospital4, Harvard University5, University of Strasbourg6, Tohoku University7, University of Texas Southwestern Medical Center8, Walton Centre9, Heidelberg University10, Universidade Federal de Minas Gerais11, Johns Hopkins University12, Oregon Health & Science University13, University of British Columbia14, University of Oxford15
TL;DR: The International Panel for NMO Diagnosis (IPND) was convened to develop revised diagnostic criteria using systematic literature reviews and electronic surveys to facilitate consensus and achieved consensus on pediatric NMOSD diagnosis and the concepts of monophasicNMOSD and opticospinal MS.
Abstract: Neuromyelitis optica (NMO) is an inflammatory CNS syndrome distinct from multiple sclerosis (MS) that is associated with serum aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). Prior NMO diagnostic criteria required optic nerve and spinal cord involvement but more restricted or more extensive CNS involvement may occur. The International Panel for NMO Diagnosis (IPND) was convened to develop revised diagnostic criteria using systematic literature reviews and electronic surveys to facilitate consensus. The new nomenclature defines the unifying term NMO spectrum disorders (NMOSD), which is stratified further by serologic testing (NMOSD with or without AQP4-IgG). The core clinical characteristics required for patients with NMOSD with AQP4-IgG include clinical syndromes or MRI findings related to optic nerve, spinal cord, area postrema, other brainstem, diencephalic, or cerebral presentations. More stringent clinical criteria, with additional neuroimaging findings, are required for diagnosis of NMOSD without AQP4-IgG or when serologic testing is unavailable. The IPND also proposed validation strategies and achieved consensus on pediatric NMOSD diagnosis and the concepts of monophasic NMOSD and opticospinal MS.
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University College London1, Children's Hospital of Philadelphia2, VU University Medical Center3, Sir Charles Gairdner Hospital4, National Multiple Sclerosis Society5, Vita-Salute San Raffaele University6, Medical University of Graz7, Ottawa Hospital Research Institute8, Fukushima Medical University9, New York University10, University of Düsseldorf11, University of Basel12, Corinne Goldsmith Dickinson Center for Multiple Sclerosis13, University of Manitoba14, St. Michael's Hospital15, Hebron University16, Johns Hopkins University17, University of Copenhagen18, University of British Columbia19, University of Bari20, Claude Bernard University Lyon 121, French Institute of Health and Medical Research22, University of California, San Francisco23, Mayo Clinic24, Salisbury University25, Cleveland Clinic26
TL;DR: The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical clinically isolated syndrome, define what is needed to fulfil dissemination in time and space of lesions in the CNS, and stress the need for no better explanation for the presentation.
Abstract: The 2010 McDonald criteria for the diagnosis of multiple sclerosis are widely used in research and clinical practice. Scientific advances in the past 7 years suggest that they might no longer provide the most up-to-date guidance for clinicians and researchers. The International Panel on Diagnosis of Multiple Sclerosis reviewed the 2010 McDonald criteria and recommended revisions. The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical clinically isolated syndrome, define what is needed to fulfil dissemination in time and space of lesions in the CNS, and stress the need for no better explanation for the presentation. The following changes were made: in patients with a typical clinically isolated syndrome and clinical or MRI demonstration of dissemination in space, the presence of CSF-specific oligoclonal bands allows a diagnosis of multiple sclerosis; symptomatic lesions can be used to demonstrate dissemination in space or time in patients with supratentorial, infratentorial, or spinal cord syndrome; and cortical lesions can be used to demonstrate dissemination in space. Research to further refine the criteria should focus on optic nerve involvement, validation in diverse populations, and incorporation of advanced imaging, neurophysiological, and body fluid markers.
3,945 citations
TL;DR: The Eighth Edition of the JCA Special Issue seeks to continue to serve as a key resource that guides the utilization of TA in the treatment of human disease.
Abstract: The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating, and categorizing indications for the evidence-based use of therapeutic apheresis in human disease. Since the 2007 JCA Special Issue (Fourth Edition), the Committee has incorporated systematic review and evidence-based approaches in the grading and categorization of apheresis indications. This Seventh Edition of the JCA Special Issue continues to maintain this methodology and rigor to make recommendations on the use of apheresis in a wide variety of diseases/conditions. The JCA Seventh Edition, like its predecessor, has consistently applied the category and grading system definitions in the fact sheets. The general layout and concept of a fact sheet that was used since the fourth edition has largely been maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis in a specific disease entity. The Seventh Edition discusses 87 fact sheets (14 new fact sheets since the Sixth Edition) for therapeutic apheresis diseases and medical conditions, with 179 indications, which are separately graded and categorized within the listed fact sheets. Several diseases that are Category IV which have been described in detail in previous editions and do not have significant new evidence since the last publication are summarized in a separate table. The Seventh Edition of the JCA Special Issue serves as a key resource that guides the utilization of therapeutic apheresis in the treatment of human disease. J. Clin. Apheresis 31:149-162, 2016. © 2016 Wiley Periodicals, Inc.
1,691 citations
TL;DR: The predominantly relapsing and often severe disease course and the short median time to second attack support the use of prophylactic long-term treatments in patients with MOG-IgG-positive ON and/or myelitis; however, treatment failure leading to rapid accumulation of disability was noted in many patients as well as flare-ups after steroid withdrawal.
Abstract: A subset of patients with neuromyelitis optica spectrum disorders (NMOSD) has been shown to be seropositive for myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) To describe the epidemiological, clinical, radiological, cerebrospinal fluid (CSF), and electrophysiological features of a large cohort of MOG-IgG-positive patients with optic neuritis (ON) and/or myelitis (n = 50) as well as attack and long-term treatment outcomes Retrospective multicenter study The sex ratio was 1:28 (m:f) Median age at onset was 31 years (range 6-70) The disease followed a multiphasic course in 80% (median time-to-first-relapse 5 months; annualized relapse rate 092) and resulted in significant disability in 40% (mean follow-up 75 ± 465 months), with severe visual impairment or functional blindness (36%) and markedly impaired ambulation due to paresis or ataxia (25%) as the most common long-term sequelae Functional blindness in one or both eyes was noted during at least one ON attack in around 70% Perioptic enhancement was present in several patients Besides acute tetra-/paraparesis, dysesthesia and pain were common in acute myelitis (70%) Longitudinally extensive spinal cord lesions were frequent, but short lesions occurred at least once in 44% Fourty-one percent had a history of simultaneous ON and myelitis Clinical or radiological involvement of the brain, brainstem, or cerebellum was present in 50%; extra-opticospinal symptoms included intractable nausea and vomiting and respiratory insufficiency (fatal in one) CSF pleocytosis (partly neutrophilic) was present in 70%, oligoclonal bands in only 13%, and blood-CSF-barrier dysfunction in 32% Intravenous methylprednisolone (IVMP) and long-term immunosuppression were often effective; however, treatment failure leading to rapid accumulation of disability was noted in many patients as well as flare-ups after steroid withdrawal Full recovery was achieved by plasma exchange in some cases, including after IVMP failure Breakthrough attacks under azathioprine were linked to the drug-specific latency period and a lack of cotreatment with oral steroids Methotrexate was effective in 5/6 patients Interferon-beta was associated with ongoing or increasing disease activity Rituximab and ofatumumab were effective in some patients However, treatment with rituximab was followed by early relapses in several cases; end-of-dose relapses occurred 9-12 months after the first infusion Coexisting autoimmunity was rare (9%) Wingerchuk’s 2006 and 2015 criteria for NMO(SD) and Barkhof and McDonald criteria for multiple sclerosis (MS) were met by 28%, 32%, 15%, 33%, respectively; MS had been suspected in 36% Disease onset or relapses were preceded by infection, vaccination, or pregnancy/delivery in several cases Our findings from a predominantly Caucasian cohort strongly argue against the concept of MOG-IgG denoting a mild and usually monophasic variant of NMOSD The predominantly relapsing and often severe disease course and the short median time to second attack support the use of prophylactic long-term treatments in patients with MOG-IgG-positive ON and/or myelitis
671 citations
Cites background or methods from "International consensus diagnostic ..."
...longitudinally extensive (more than half the length of the corpus callosum), as considered typical for AQP4IgG-positive NMOSD [29], in 1/8 (12....
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...%) patients met the 2015 international consensus criteria for NMOSD [29] (Table 1)....
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...Both LEON lesions and chiasmatic lesions were previously thought to be indicative of (AQP4-IgG-positive) NMOSD [29]....
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...Other suspected diagnoses included acute disseminated EM (ADEM), multiphasic disseminated EM, AQP4-IgG-negative NMO according to Wingerchuk’s 2006 criteria [28], AQP4-IgGnegative NMOSD according to the 2015 international diagnostic consensus criteria [29], viral encephalitis, bacterial encephalitis, paraneoplastic encephalitis, isolated vasculitis of the CNS, chronic relapsing inflammatory optic neuropathy (CRION), CNS lymphoma, sarcoidosis, spinal stenosis, “spinal tumor of unknown dignity”, suspected spinal ischemia, para- or postinfectious ON, and myelitis; some patients were diagnosed with ON, rON, (longitudinally extensive transverse) myelitis, brainstem encephalitis or EM “of unknown origin”....
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...Keywords: Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG), Autoantibodies, Neuromyelitis optica spectrum disorders (NMOSD), Aquaporin-4 antibodies (AQP4-IgG, NMO-IgG), Optic neuritis, Transverse myelitis, Longitudinally extensive transverse myelitis, Magnetic resonance imaging, Cerebrospinal fluid, Oligoclonal bands, Electrophysiology, Evoked potentials, Treatment, Therapy, Methotrexate, Azathioprine, Rituximab, Ofatumumab, Interferon beta, Glatiramer acetate, Natalizumab, Outcome, Pregnancy, Infections, Vaccination, Multiple sclerosis, Barkhof criteria, McDonald criteria, Wingerchuk criteria 2006 and 2015, IPND criteria, International consensus diagnostic criteria for neuromyelitis optica spectrum disorders...
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Vita-Salute San Raffaele University1, National Institute for Health Research2, UCL Institute of Neurology3, University of Siena4, University of Nottingham5, University of Basel6, Autonomous University of Barcelona7, University of Copenhagen8, University of Oxford9, National Institutes of Health10, Children's Hospital of Philadelphia11, VU University Amsterdam12
TL;DR: State-of-the-art MRI findings in patients presenting with a clinically isolated syndrome were discussed in a MAGNIMS workshop, the goal of which was to provide an evidence-based and expert-opinion consensus on diagnostic MRI criteria modifications.
Abstract: In patients presenting with a clinically isolated syndrome, MRI can support and substitute clinical information in the diagnosis of multiple sclerosis by showing disease dissemination in space and time and by helping to exclude disorders that can mimic multiple sclerosis. MRI criteria were first included in the diagnostic work-up for multiple sclerosis in 2001, and since then several modifications to the criteria have been proposed in an attempt to simplify lesion-count models for showing disease dissemination in space, change the timing of MRI scanning to show dissemination in time, and increase the value of spinal cord imaging. Since the last update of these criteria, new data on the use of MRI to establish dissemination in space and time have become available, and MRI technology has improved. State-of-the-art MRI findings in these patients were discussed in a MAGNIMS workshop, the goal of which was to provide an evidence-based and expert-opinion consensus on proposed modifications to MRI criteria for the diagnosis of multiple sclerosis.
627 citations
TL;DR: Criteria for neuromyelitis optica (NMO) spectrum disorders (NMOSD) was proposed that incorporated unifying the terms NMO and NMOSD, including patients with aquaporin-4 (AQP4)–immunoglobulin G (IgG) negative/unknown, thus giving these patients …
Abstract: Editors' Note: The international consensus diagnostic criteria for neuromyelitis optica spectrum disorders (NMOSD) article prompted reactions from our readers. Tan is concerned that the new criteria may include patients without true neuromyelitis optica and may affect treatment funding. Recounting their own experience, Mao et al. caution about overinterpretation of MRI results and suggest that aquaporin-4 antibody (AQP4-Ab) testing be considered in late-onset demyelinating disease. In response, Wingerchuk et al., authors of the guidelines, stress that the diagnostic category of NMOSD without AQP4–immunoglobulin G requires exclusion of alternative diagnoses, believe that the new criteria will facilitate—rather than hinder—insurance coverage for appropriate immunosuppressive treatments, and agree with the observations raised by Mao et al. —Chafic Karam, MD, and Robert C. Griggs, MD
Wingerchuk et al.1 proposed criteria for neuromyelitis optica (NMO) spectrum disorders (NMOSD) that incorporated unifying the terms NMO and NMOSD, including patients with aquaporin-4 (AQP4)–immunoglobulin G (IgG) negative/unknown, thus giving these patients …
510 citations
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TL;DR: The case of a patient who developed extensive brain lesions during fingolimod (FTY720) treatment in the TRANSFORMS study, who had residual encephalomalacia and no recurrence with steroid treatment over 3 years following withdrawal of fingolIMod.
Abstract: We report the case of a patient who developed extensive brain lesions during fingolimod (FTY720) treatment in the TRANSFORMS study. His initial diagnosis was multiple sclerosis, but after encephalopathy anti-aquaporin4 antibody (anti-AQP4 Ab) was detected, it was changed to neuromyelitis optica spectrum disorder. After treatment with fingolimod, he developed bilateral extensive brain lesions. The brain MRI showed lesions predominantly involving the right frontal and parietal lobes, with vasogenic edema and enhancement. He had residual encephalomalacia and no recurrence with steroid treatment over 3 years following withdrawal of fingolimod.
249 citations
TL;DR: The similar frequency of neuromyelitis optica (NMO)-IgG in both childhood and adult cases of NMO, and its rarity in relapsing-remitting multiple sclerosis, supports the concept that these diseases have a similar pathogenesis in childhood and adulthood.
Abstract: Objective: To determine seroprevalence of neuromyelitis optica (NMO)-IgG in childhood CNS inflammatory demyelinating disorders. Methods: We analyzed demographic, clinical, and radiologic data in a blinded fashion and assessed serum NMO-IgG status for 87 children: 41 with relapsing-remitting multiple sclerosis (RRMS), 17 with NMO, 13 with monophasic/recurrent optic neuritis (ON), 13 with transverse myelitis, of whom 10 were longitudinally extensive on MRI spine (LETM), and another 3 with LETM in the context of acute disseminated encephalomyelitis (ADEM). Results: Ten of the 87 children (11%) were seropositive. Eight of 17 with NMO (47%) were seropositive (7 of 9 with relapsing NMO [78%], 1 of 8 with monophasic NMO [12.5%]). Two other children were seropositive: 1 of 5 with recurrent ON and one child with recurrent LETM. No seropositive case was identified among 41 with RRMS (14% of whom had LETM at some point in their clinical course), 8 with monophasic ON, 9 with monophasic LETM, or 3 with LETM in the context of ADEM. Conclusions: The similar frequency of neuromyelitis optica (NMO)-IgG in both childhood and adult cases of NMO, and its rarity in relapsing-remitting multiple sclerosis, supports the concept that these diseases have a similar pathogenesis in childhood and adulthood. It is noteworthy that none of nine children with monophasic longitudinally extensive transverse myelitis (LETM) was NMO-IgG-seropositive. Furthermore, LETM does not appear to be as predictive of an NMO spectrum disorder in children as it is in adults. Longitudinal studies of larger pediatric LETM cohorts are required to ascertain whether the absence of NMO-IgG is a negative predictor for relapse in this childhood entity. GLOSSARY: ADEM = acute disseminated encephalomyelitis; EDSS = Expanded Disability Status Scale; LETM = longitudinally extensive transverse myelitis; NMO = neuromyelitis optica; ON = optic neuritis; RRMS = relapsing-remitting multiple sclerosis; TM = transverse myelitis.
241 citations
"International consensus diagnostic ..." refers background in this paper
...Approximately 15% of children with MS may have LETM during relapse, LETM can accompany monophasic ADEM, and AQP4-IgG is rarely detected in children with monophasic LETM.55 In children diagnosed with ADEM according to international consensus criteria, which require a polyfocal demyelinating clinical presentation with encephalopathy,57 the presence of AQP4-IgG favors a diagnosis of NMOSD, although prospective validation studies are required to determine risk of recurrent NMOSD events....
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...Approximately 15% of children with MS may have LETM during relapse, LETM can accompany monophasic ADEM, and AQP4-IgG is rarely detected in children with monophasic LETM.(55) In children diagnosed with ADEM according to international consensus criteria, which require a polyfocal demyelinating clinical presentation with encephalopathy,(57) the presence of AQP4-IgG favors a diagnosis of NMOSD, although prospective validation studies are required to determine risk of recurrent NMOSD events....
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TL;DR: Despite being a rare disease, NMO is more common in a Caucasian population than earlier believed and is estimated to be 0.4 per 105 person-years in the population annually.
Abstract: Background: Epidemiologic studies have suggested different prevalence of neuromyelitis optica (NMO) in different ethnic groups. However, data on the incidence and prevalence of NMO in Caucasians are scarce. Objective: To estimate the incidence and prevalence of NMO in a predominantly Caucasian population based on the Wingerchuk 2006 criteria. Methods: The study was a population-based retrospective case series with longitudinal follow-up. Patients with multiple sclerosis (MS), optic neuritis (ON), acute transverse myelitis (TM), and NMO from the 4 neurology and 3 ophthalmology departments in the Region of Southern Denmark having been diagnosed between 1998 and 2008 were investigated. Patients were included based on 1) episodes of ON or TM and 2) an initial brain MRI not diagnostic for MS. An immunofluorescence assay was used to determine aquaporin-4 (AQP-4) antibodies. Results: A total of 477 patients with MS, TM, or ON were evaluated: 163 fulfilled the inclusion criteria, 42 (26%) qualified for the diagnosis of NMO, 26 (62.0%) of these were AQP4 antibody positive. All except one were Caucasian, the female:male ratio was 2.8:1, and mean age at onset was 35.6 years (range 15–64 years). The clinical presentation was heterogeneous including TM, longitudinally extensive TM, ON, and brainstem syndromes. The yearly incidence rate of NMO in the population was estimated to be 0.4 per 10 5 person-years (95% confidence interval [CI] 0.30–0.54) and the prevalence was 4.4 per 10 5 (95% CI 3.1–5.7). Conclusions: Despite being a rare disease, NMO is more common in a Caucasian population than earlier believed.
232 citations
TL;DR: In this article, a comprehensively review and critically appraise the existing literature on NMO‐IgG/AQP4‐Ab testing and recommendations for the clinical application of N MO‐IGG/ aQP 4‐Ab serology are given.
Abstract: Antibodies to aquaporin-4 (called NMO-IgG or AQP4-Ab) constitute a sensitive and highly specific serum marker of neuromyelitis optica (NMO) that can facilitate the differential diagnosis of NMO and classic multiple sclerosis. NMO-IgG/AQP4-Ab seropositive status has also important prognostic and therapeutic implications in patients with isolated longitudinally extensive myelitis (LETM) or optic neuritis (ON). In this article, we comprehensively review and critically appraise the existing literature on NMO-IgG/AQP4-Ab testing. All available immunoassays-including tissue-based (IHC), cell-based (ICC, FACS) and protein-based (RIPA, FIPA, ELISA, Western blotting) assays-and their differential advantages and disadvantages are discussed. Estimates for sensitivity, specificity, and positive and negative likelihood ratios are calculated for all published studies and accuracies of the various immunoassay techniques compared. Subgroup analyses are provided for NMO, LETM and ON, for relapsing vs. monophasic disease, and for various control groups (eg, MS vs. other controls). Numerous aspects of NMO-IgG/AQP4-Ab testing relevant for clinicians (eg, impact of antibody titers and longitudinal testing, indications for repeat testing, relevance of CSF testing and subclass analysis, NMO-IgG/AQP4-Ab in patients with rheumatic diseases) as well as technical aspects (eg, AQP4-M1 vs. AQP4-M23-based assays, intact AQP4 vs. peptide substrates, effect of storage conditions and freeze/thaw cycles) and pitfalls are discussed. Finally, recommendations for the clinical application of NMO-IgG/AQP4-Ab serology are given.
227 citations
Johns Hopkins University1, Tohoku University2, Walton Centre3, Universidade Federal de Minas Gerais4, University of Oxford5, University of Lyon6, University of Strasbourg7, University of Texas Southwestern Medical Center8, University of British Columbia9, University of California, San Francisco10, Mayo Clinic11
TL;DR: This review provides a comprehensive analysis of each of these medications in NMO and concludes with a set of recommended consensus practices.
Abstract: Neuromyelitis optica (NMO) is an autoimmune demyelinating disease preferentially targeting the optic nerves and spinal cord. Once regarded as a variant of multiple sclerosis (MS), NMO is now recognized to be a different disease with unique pathology and immunopathogenesis that does not respond to traditional MS immunomodulators such as interferons. Preventive therapy in NMO has focused on a range of immunosuppressive medications, none of which have been validated in a rigorous randomized trial. However, multiple retrospective and a few recent prospective studies have provided evidence for the use of six medications for the prevention of NMO exacerbations: azathioprine, rituximab, mycophenolate mofetil, prednisone, methotrexate and mitoxantrone. This review provides a comprehensive analysis of each of these medications in NMO and concludes with a set of recommended consensus practices.
219 citations