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Journal of Neurology Jul 2023The term 'neuromyelitis optica spectrum disorders' (NMOSD) is used as an umbrella term that refers to aquaporin-4 immunoglobulin G (AQP4-IgG)-positive neuromyelitis... (Review)
Review
Update on the diagnosis and treatment of neuromyelits optica spectrum disorders (NMOSD) - revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part I: Diagnosis and differential diagnosis.
The term 'neuromyelitis optica spectrum disorders' (NMOSD) is used as an umbrella term that refers to aquaporin-4 immunoglobulin G (AQP4-IgG)-positive neuromyelitis optica (NMO) and its formes frustes and to a number of closely related clinical syndromes without AQP4-IgG. NMOSD were originally considered subvariants of multiple sclerosis (MS) but are now widely recognized as disorders in their own right that are distinct from MS with regard to immunopathogenesis, clinical presentation, optimum treatment, and prognosis. In part 1 of this two-part article series, which ties in with our 2014 recommendations, the neuromyelitis optica study group (NEMOS) gives updated recommendations on the diagnosis and differential diagnosis of NMOSD. A key focus is on differentiating NMOSD from MS and from myelin oligodendrocyte glycoprotein antibody-associated encephalomyelitis (MOG-EM; also termed MOG antibody-associated disease, MOGAD), which shares significant similarity with NMOSD with regard to clinical and, partly, radiological presentation, but is a pathogenetically distinct disease. In part 2, we provide updated recommendations on the treatment of NMOSD, covering all newly approved drugs as well as established treatment options.
Topics: Humans; Neuromyelitis Optica; Diagnosis, Differential; Myelin-Oligodendrocyte Glycoprotein; Aquaporin 4; Multiple Sclerosis; Immunoglobulin G; Autoantibodies
PubMed: 37022481
DOI: 10.1007/s00415-023-11634-0 -
Clinical Medicine (London, England) Mar 2019Neuromyelitis optica spectrum disorder (NMOSD) is an uncommon antibody-mediated disease of the central nervous system. Long segments of spinal cord inflammation... (Review)
Review
Neuromyelitis optica spectrum disorder (NMOSD) is an uncommon antibody-mediated disease of the central nervous system. Long segments of spinal cord inflammation (myelitis), severe optic neuritis, and/or bouts of intractable vomiting and hiccoughs (area postrema syndrome) are classic presentations of the disease and may alert the clinician to the diagnosis. Untreated, approximately 50% of NMOSD patients will be wheelchair users and blind, and a third will have died within 5 years of their first attack. Unlike multiple sclerosis, a progressive clinical course is very unusual and the accrual of disability is related to relapses. Approximately 75% of patients have antibodies against aquaporin-4, a water channel expressed on astrocytes. Relapses are treated aggressively to prevent residual disability with high-dose steroids and often plasma exchange. Relapse prevention is crucial and achieved with long-term immunosuppression. In this article we review the pathogenesis, clinical features, diagnosis and management of NMOSD.
Topics: Adult; Aquaporin 4; Autoantibodies; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Neuromyelitis Optica; Young Adult
PubMed: 30872305
DOI: 10.7861/clinmedicine.19-2-169 -
Neurology Jul 2015Neuromyelitis optica (NMO) is an inflammatory CNS syndrome distinct from multiple sclerosis (MS) that is associated with serum aquaporin-4 immunoglobulin G antibodies...
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.
Topics: Humans; Neuromyelitis Optica
PubMed: 26092914
DOI: 10.1212/WNL.0000000000001729 -
Journal of Neurology Jan 2024This manuscript presents practical recommendations for managing acute attacks and implementing preventive immunotherapies for neuromyelitis optica spectrum disorders... (Review)
Review
Update on the diagnosis and treatment of neuromyelitis optica spectrum disorders (NMOSD) - revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part II: Attack therapy and long-term management.
This manuscript presents practical recommendations for managing acute attacks and implementing preventive immunotherapies for neuromyelitis optica spectrum disorders (NMOSD), a rare autoimmune disease that causes severe inflammation in the central nervous system (CNS), primarily affecting the optic nerves, spinal cord, and brainstem. The pillars of NMOSD therapy are attack treatment and attack prevention to minimize the accrual of neurological disability. Aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) are a diagnostic marker of the disease and play a significant role in its pathogenicity. Recent advances in understanding NMOSD have led to the development of new therapies and the completion of randomized controlled trials. Four preventive immunotherapies have now been approved for AQP4-IgG-positive NMOSD in many regions of the world: eculizumab, ravulizumab - most recently-, inebilizumab, and satralizumab. These new drugs may potentially substitute rituximab and classical immunosuppressive therapies, which were as yet the mainstay of treatment for both, AQP4-IgG-positive and -negative NMOSD. Here, the Neuromyelitis Optica Study Group (NEMOS) provides an overview of the current state of knowledge on NMOSD treatments and offers statements and practical recommendations on the therapy management and use of all available immunotherapies for this disease. Unmet needs and AQP4-IgG-negative NMOSD are also discussed. The recommendations were developed using a Delphi-based consensus method among the core author group and at expert discussions at NEMOS meetings.
Topics: Humans; Neuromyelitis Optica; Aquaporin 4; Spinal Cord; Central Nervous System; Autoantibodies; Immunoglobulin G
PubMed: 37676297
DOI: 10.1007/s00415-023-11910-z -
Nature Reviews. Immunology Dec 2021The realization that autoantibodies can contribute to dysfunction of the brain has brought about a paradigm shift in neurological diseases over the past decade, offering... (Review)
Review
The realization that autoantibodies can contribute to dysfunction of the brain has brought about a paradigm shift in neurological diseases over the past decade, offering up important novel diagnostic and therapeutic opportunities. Detection of specific autoantibodies to neuronal or glial targets has resulted in a better understanding of central nervous system autoimmunity and in the reclassification of some diseases previously thought to result from infectious, 'idiopathic' or psychogenic causes. The most prominent examples, such as aquaporin 4 autoantibodies in neuromyelitis optica or NMDAR autoantibodies in encephalitis, have stimulated an entire field of clinical and experimental studies on disease mechanisms and immunological abnormalities. Also, these findings inspired the search for additional autoantibodies, which has been very successful to date and has not yet reached its peak. This Review summarizes this rapid development at a point in time where preclinical studies have started delivering fundamental new data for mechanistic understanding, where new technologies are being introduced into this field, and - most importantly - where the first specifically tailored immunotherapeutic approaches are emerging.
Topics: Animals; Aquaporin 4; Autoantibodies; Autoimmunity; Brain; Encephalitis; Humans; Neuromyelitis Optica; Receptors, N-Methyl-D-Aspartate
PubMed: 33976421
DOI: 10.1038/s41577-021-00543-w -
Multiple Sclerosis (Houndmills,... Oct 2023Most patients with neuromyelitis optica spectrum disorders (NMOSD) test positive for aquaporin-4 antibody (AQP4-IgG) or myelin oligodendrocyte glycoprotein antibodies... (Review)
Review
Most patients with neuromyelitis optica spectrum disorders (NMOSD) test positive for aquaporin-4 antibody (AQP4-IgG) or myelin oligodendrocyte glycoprotein antibodies (MOG-IgG). Those who are negative are termed double-negative (DN) NMOSD and may constitute a diagnostic and therapeutic challenge. DN NMOSD is a syndrome rather than a single disease, ranging from a (postinfectious) monophasic illness to a more chronic syndrome that can be indistinguishable from AQP4-IgG+ NMOSD or develop into other mimics such as multiple sclerosis. Thus, underlying disease mechanisms are likely to be heterogeneous. This topical review aims to (1) reappraise antibody-negative NMOSD definition as it has changed over time with the development of the AQP4 and MOG-IgG assays; (2) outline clinical characteristics and the pathophysiological nature of this rare entity by contrasting its differences and similarities with antibody-positive NMOSD; (3) summarize laboratory characteristics and magnetic resonance imaging findings of DN NMOSD; and (4) discuss the current treatment for DN NMOSD.
Topics: Humans; Neuromyelitis Optica; Aquaporin 4; Myelin-Oligodendrocyte Glycoprotein; Immunoglobulin G; Multiple Sclerosis; Autoantibodies
PubMed: 37740717
DOI: 10.1177/13524585231199819 -
Current Opinion in Ophthalmology Nov 2020Neuromyelitis optica spectrum disorder is an autoimmune disease that causes optic neuritis and transverse myelitis. Attacks can cause severe neurological damage leading... (Review)
Review
PURPOSE OF REVIEW
Neuromyelitis optica spectrum disorder is an autoimmune disease that causes optic neuritis and transverse myelitis. Attacks can cause severe neurological damage leading to blindness and paralysis. Understanding of the immunopathogenesis of this disease has led to major breakthroughs in diagnosis and treatment. In the past 18 months, three successful phase 3 clinical trials have been published using targeted approaches to preventing relapses.
RECENT FINDINGS
Updates in epidemiology, imaging, quality of life and treatment for acute relapse and prevention have been published in the past 18 months. Epidemiology studies are distinguishing patients based on their antigen specificity for aquaporin-4 and myelin oligodendrocyte glycoprotein, which are increasingly recognized as separate immunological conditions. Imaging by MRI and optical coherence tomography continue to be developed as tools to distinguish neuromyelitis optica spectrum disorders (NMOSD) from other diseases. This is especially relevant as the recent clinical trials showed differences in response between aquaporin-4 seropositive and seronegative patients. The three drugs that were tested for prevention of NMOSD relapses were eculizumab, inebilizumab, and satralizumab. All of the trials were worldwide, placebo-controlled, double-masked studies that demonstrated a clear benefit with each approach.
SUMMARY
Recent research in NMOSD has resulted in improved diagnosis and approved treatments.
Topics: Animals; Aquaporin 4; Humans; Neuromyelitis Optica; Optic Neuritis; Quality of Life; Recurrence; Secondary Prevention
PubMed: 33009077
DOI: 10.1097/ICU.0000000000000703 -
International Journal of Molecular... Aug 2021Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune central nervous system (CNS) inflammatory disorder that can lead to serious disability and mortality.... (Review)
Review
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune central nervous system (CNS) inflammatory disorder that can lead to serious disability and mortality. Females are predominantly affected, including those within the reproductive age. Most patients develop relapsing attacks of optic neuritis; longitudinally extensive transverse myelitis; and encephalitis, especially brainstem encephalitis. The majority of NMOSD patients are seropositive for IgG autoantibodies against the water channel protein aquaporin-4 (AQP4-IgG), reflecting underlying aquaporin-4 autoimmunity. Histological findings of the affected CNS tissues of patients from in-vitro and in-vivo studies support that AQP4-IgG is directly pathogenic in NMOSD. It is believed that the binding of AQP4-IgG to CNS aquaporin-4 (abundantly expressed at the endfoot processes of astrocytes) triggers astrocytopathy and neuroinflammation, resulting in acute attacks. These attacks of neuroinflammation can lead to pathologies, including aquaporin-4 loss, astrocytic activation, injury and loss, glutamate excitotoxicity, microglial activation, neuroinflammation, demyelination, and neuronal injury, via both complement-dependent and complement-independent pathophysiological mechanisms. With the increased understanding of these mechanisms underlying this serious autoimmune astrocytopathy, effective treatments for both active attacks and long-term immunosuppression to prevent relapses in NMOSD are increasingly available based on the evidence from retrospective observational data and prospective clinical trials. Knowledge on the indications and potential side effects of these medications are essential for a clear evaluation of the potential benefits and risks to NMOSD patients in a personalized manner. Special issues such as pregnancy and the coexistence of other autoimmune diseases require additional concern and meticulous care. Future directions include the identification of clinically useful biomarkers for the prediction of relapse and monitoring of the therapeutic response, as well as the development of effective medications with minimal side effects, especially opportunistic infections complicated by long-term immunosuppression.
Topics: Aquaporin 4; Autoantibodies; Biomarkers; Humans; Immunosuppression Therapy; Neuromyelitis Optica
PubMed: 34445343
DOI: 10.3390/ijms22168638 -
Journal of Neurology May 2019Myelin oligodendrocyte glycoprotein (MOG) antibody disease (MOG-AD) is now recognised as a nosological entity with specific clinical and paraclinical features to aid... (Review)
Review
Myelin oligodendrocyte glycoprotein (MOG) antibody disease (MOG-AD) is now recognised as a nosological entity with specific clinical and paraclinical features to aid early diagnosis. Although no age group is exempt, median age of onset is within the fourth decade of life, with optic neuritis being the most frequent presenting phenotype. Disease course can be either monophasic or relapsing, with subsequent relapses most commonly involving the optic nerve. Residual disability develops in 50-80% of patients, with transverse myelitis at onset being the most significant predictor of long-term outcome. Recent advances in MOG antibody testing offer improved sensitivity and specificity. To avoid misdiagnosis, MOG antibody testing should be undertaken in selected cases presenting clinical and paraclinical features that are felt to be in keeping with MOG-AD, using a validated cell-based assay. MRI characteristics can help in differentiating MOG-AD from other neuroinflammatory disorders, including multiple sclerosis and neuromyelitis optica. Cerebrospinal fluid oligoclonal bands are uncommon. Randomised control trials are limited, but observational open-label experience suggests a role for high-dose steroids and plasma exchange in the treatment of acute attacks, and for immunosuppressive therapies, such as steroids, oral immunosuppressants and rituximab as maintenance treatment.
Topics: Antibodies; Aquaporin 4; Humans; Myelin-Oligodendrocyte Glycoprotein; Neuromyelitis Optica; Optic Neuritis; Plasma Exchange; Steroids
PubMed: 30569382
DOI: 10.1007/s00415-018-9122-2 -
CNS Neuroscience & Therapeutics Jul 2022Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune inflammatory demyelinating disorder of the central nervous system (CNS), which is a severely... (Review)
Review
Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune inflammatory demyelinating disorder of the central nervous system (CNS), which is a severely disabling disorder leading to devastating sequelae or even death. Repeated acute attacks and the presence of aquaporin-4 immunoglobulin G (AQP4-IgG) antibody are the typical characteristics of NMOSD. Recently, the phase III trials of the newly developed biologicals therapies have shown their effectiveness and good tolerance to a certain extent when compared with the traditional therapy with the first- and second-line drugs. However, there is still a lack of large sample, double-blind, randomized, clinical studies to confirm their efficacy, safety, and tolerability. Especially, these drugs have no clear effect on NMOSD patients without AQP4-IgG and refractory patients. Therefore, it is of strong demand to further conduct large sample, double-blind, randomized, clinical trials, and novel therapeutic possibilities in NMOSD are discussed briefly here.
Topics: Aquaporin 4; Autoantibodies; Disease Progression; Humans; Immunoglobulin G; Neuromyelitis Optica; Randomized Controlled Trials as Topic
PubMed: 35426485
DOI: 10.1111/cns.13836