Treatment of neuromyelitis optica: Review and recommendations

Kimbrough, Dorlan; Fujihara, Kazuo; Jacob, Anu; Lana-Peixoto, Marco Aurélio; Leite, Maria Isabel; Lévy, Michaël; Marignier, Romain; Nakashima, Ichiro; Palace, Jacqueline; Seze, J. de; Stüve, Olaf; Tenembaum, Sílvia; Traboulsee, Anthony; Waubant, Emmanuelle; Weinshenker, Brian G.; Wingerchuk, Dean M.

doi:10.1016/j.msard.2012.06.002

Cited by 227 publications

(222 citation statements)

References 56 publications

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“…First, neuromyelitis optica with aquaporin 4 antibodies is a highly disabling relapsing condition with predominantly white matter lesions in the spinal cord, brain, and optic nerves that needs to be distinguished from MS. Because disability accrues with each relapse, it must be treated effectively. The antibodies lead to loss of aquaporin 4 from the astrocytes in vitro, but in vivo the predominant mechanism is complement-dependent damage (see Kimbrough et al [56] for a review). Other patients, often with optic neuritis, have antibodies to myelin oligodendrocyte glycoprotein, which, if measured by IgG-specific assays, appear to distinguish these patients from MS [57].…”

Section: Antibodies To Identified Cns Proteinsmentioning

confidence: 99%

Neuroinflammation: Ways in Which the Immune System Affects the Brain

et al. 2015

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Neuroinflammation is the response of the central nervous system (CNS) to disturbed homeostasis and typifies all neurological diseases. The main reactive components of the CNS include microglial cells and infiltrating myeloid cells, astrocytes, oligodendrocytes, and the blood-brain b a r r i e r , c y t o k i n e s , a n d c y t o k i n e s i g n a l i n g . Neuroinflammatory responses may be helpful or harmful, as mechanisms associated with neuroinflammation are involved in normal brain development, as well as in neuropathological processes. This review examines the roles of various cell types that contribute to the immune dysregulation associated with neuroinflammation. Microglia enter the CNS very early in embryonic development and, as such, play an essential role in both the healthy and diseased brain. B-cell diversity contributes to CNS disease through both antibody-dependent and antibody-independent mechanisms. The influences of these B-cell mechanisms on other cell types, including myeloid cells and T cells, are reviewed in relationship to antibody-mediated CNS disorders, paraneoplastic neurological diseases, and multiple sclerosis. New insights into neuroinflammation offer exciting opportunities to investigate potential therapeutic targets for debilitating CNS diseases.

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Section: Antibodies To Identified Cns Proteinsmentioning

confidence: 99%

Neuroinflammation: Ways in Which the Immune System Affects the Brain

et al. 2015

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“…Acute exacerbations of NMOSD are usually treated with high-dose intravenous (IV) methylprednisolone (IVMP) at a dose of 1000 mg for 3-5 days with or without oral tapering [8,[24][25][26]. It has been shown that each, a first, second, and third course of IVMP significantly improves clinical disability in patients with MS and NMOSD [34], and that early administration is associated with preservation of the retinal nerve fiber layer thickness in NMOSD [35].…”

Section: Treatment Of Nmosd Attacksmentioning

confidence: 99%

“…When remission is absent or insufficient, therapeutic plasma exchange (TPE; 5-7 cycles) should be used [8,[24][25][26]. The efficacy of TPE for relapsing-remitting MS and other inflammatory demyelinating diseases was demonstrated in a randomized, controlled trial and several uncontrolled studies [36][37][38][39][40].…”

Section: Treatment Of Nmosd Attacksmentioning

confidence: 99%

“…Resistant cases without improvement after ≥ 1 course of both IVMP and apheresis therapies have occasionally been escalated to early highly active immunotherapy such as IV cyclophosphamide [26], mitoxantrone [8], or tocilizumab [51,52], which induced a dramatic improvement in disability in single patients.…”

Section: Treatment Of Nmosd Attacksmentioning

confidence: 99%

“…Several national and international guidelines describing diagnosis and treatment of NMOSD have been published [8,[24][25][26][27]], yet most therapeutic recommendations are still expert-based because until recently all studies reporting treatment outcomes had been conducted in a nonrandomized and often retrospective setting.…”

Section: Introductionmentioning

confidence: 99%

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Present and Future Therapies in Neuromyelitis Optica Spectrum Disorders

Kleiter

Gold

2016

Neurotherapeutics

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Neuromyelitis optica spectrum disorders (NMOSD) are important evolving entities, which have reached much attention in the recent years. NMOSD are characterized by inflammatory lesions in the optic nerves, spinal cord, and central parts of the brain, as well as an autoimmune process directed against aquaporin-4. As disability in NMOSD accumulates by inflammatory damage from attacks, both the treatment and prevention of attacks are decisive for the long-term outcome. NMOSD attacks are treated with highdose intravenous corticosteroids and apheresis therapies, in particular therapeutic plasma exchange. In cases of incomplete remission, escalation of attack treatment is recommended. Preventive therapy is immunosuppressive and should by commenced as early as possible. Apart from classical immunosuppressants such as azathioprine and mycophenolate mofetil, repurposed biologicals are increasingly used. B-cell depletion with rituximab and other agents, inhibition of the interleukin-6 receptor with tocilizumab, and blockade of complement-mediated damage by eculizumab all are promising therapeutic strategies evaluated in randomized controlled trials. In this review, we will discuss present and future immunotherapies for NMOSD and also consider combination of treatments, plasma, cellular and other therapies. Current advances in immunopathological knowledge are translated into innovative concepts and begin a new era of NMOSD therapy.

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Comparison of Relapse and Treatment Failure Rates Among Patients With Neuromyelitis Optica

et al. 2014

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euromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system (CNS) distinct from multiple sclerosis (MS). It is characterized by optic neuritis (ON), longitudinally extensive transverse myelitis (TM), and, in approximately 70% of cases, the presence in serum of IgG antibodies that target aquaporin 4 (AQP4-IgG; also known as NMO-IgG). Patients with neuromyelitis optica spectrum disorder (NMOSD) are seropositive for AQP4-IgG and have evidence of an inflammatory event consistent with NMO, including TM, ON, or brainstem inflammation. Disease-modifying treatment for relapse prevention in patients with NMO and NMOSD requires immunosuppression because some immunomodulatory therapies used for MS appear to aggravate NMO. 1-3 Although no placebo-controlled or comparative randomized controlled trials of immunosuppressive therapies have been conducted for NMO and there is no consensus on how to select initial therapy, there is evidence that azathioprine, mycophenolate mofetil, and rituximab are effective in reducing relapse rates. 4-10 We conducted this retrospective study to compare relapse and treatment failure rates among NMO and NMOSD patients who received azathioprine, mycophenolate, or rituximab as their initial long-term immunosuppressive therapy at the Johns Hopkins Hospital and Mayo Clinic. Methods Institutional review board approval was obtained from the Johns Hopkins University and Mayo Clinic. Deidentified data were used; therefore, patient consent was not required. Patients were included if they were diagnosed as having NMO IMPORTANCE Neuromyelitis optica (NMO) is an inflammatory disease of the optic nerves and spinal cord that leads to blindness and paralysis. Effective immunosuppression is the standard of care for relapse prevention. OBJECTIVE To compare the relapse and treatment failure rates among patients receiving the 3 most common forms of immunosuppression for NMO: azathioprine, mycophenolate mofetil, and rituximab. DESIGN, SETTING, AND PARTICIPANTS We performed a retrospective, multicenter analysis of relapses in 90 patients with NMO and NMO spectrum disorder treated with azathioprine, mycophenolate, and/or rituximab at the Mayo Clinic and the Johns Hopkins Hospital during the past 10 years. MAIN OUTCOME AND MEASURE Annualized relapse rates. RESULTS Rituximab reduced the relapse rate up to 88.2%, with 2 in 3 patients achieving complete remission. Mycophenolate reduced the relapse rate by up to 87.4%, with a 36% failure rate. Azathioprine reduced the relapse rate by 72.1% but had a 53% failure rate despite concurrent use of prednisone. CONCLUSIONS AND RELEVANCE Initial treatment with rituximab, mycophenolate, and, to a lesser degree, azathioprine significantly reduces relapse rates in NMO and NMO spectrum disorder patients. Patients for whom initial treatment fails often achieve remission when treatment is switched from one to another of these drugs.

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Treatment of neuromyelitis optica: Review and recommendations

Cited by 227 publications

References 56 publications

Neuroinflammation: Ways in Which the Immune System Affects the Brain

Neuroinflammation: Ways in Which the Immune System Affects the Brain

Present and Future Therapies in Neuromyelitis Optica Spectrum Disorders

Comparison of Relapse and Treatment Failure Rates Among Patients With Neuromyelitis Optica

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