Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 479
Filtrar
1.
Nat Rev Neurol ; 16(3): 154-170, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32080393

RESUMO

Neuromyelitis optica spectrum disorders (NMOSD) are a type of neurological autoimmune disease characterized by attacks of CNS inflammation that are often severe and predominantly affect the spinal cord and optic nerve. The majority of individuals with NMOSD are women, many of whom are of childbearing age. Although NMOSD are rare, several small retrospective studies and case reports have indicated that pregnancy can worsen disease activity and might contribute to disease onset. NMOSD disease activity seems to negatively affect pregnancy outcomes. Moreover, some of the current NMOSD treatments are known to pose risks to the developing fetus and only limited safety data are available for others. Here, we review published studies regarding the relationship between pregnancy outcomes and NMOSD disease activity. We also assess the risks associated with using disease-modifying therapies for NMOSD during the course of pregnancy and breastfeeding. On the basis of the available evidence, we offer recommendations regarding the use of these therapies in the course of pregnancy planning in individuals with NMOSD.


Assuntos
Anormalidades Induzidas por Medicamentos , Aborto Espontâneo/induzido quimicamente , Fatores Imunológicos/efeitos adversos , Neuromielite Óptica/tratamento farmacológico , Neuromielite Óptica/imunologia , Complicações do Trabalho de Parto/induzido quimicamente , Pré-Eclâmpsia/induzido quimicamente , Adulto , Feminino , Humanos , Gravidez
2.
N Engl J Med ; 381(22): 2114-2124, 2019 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-31774956

RESUMO

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system and is associated with autoantibodies to anti-aquaporin-4 (AQP4-IgG) in approximately two thirds of patients. Interleukin-6 is involved in the pathogenesis of the disorder. Satralizumab is a humanized monoclonal antibody targeting the interleukin-6 receptor. The efficacy of satralizumab added to immunosuppressant treatment in patients with NMOSD is unclear. METHODS: In a phase 3, randomized, double-blind, placebo-controlled trial, we randomly assigned, in a 1:1 ratio, patients with NMOSD who were seropositive or seronegative for AQP4-IgG to receive either satralizumab, at a dose of 120 mg, or placebo, administered subcutaneously at weeks 0, 2, and 4 and every 4 weeks thereafter, added to stable immunosuppressant treatment. The primary end point was the first protocol-defined relapse in a time-to-event analysis. Key secondary end points were the change from baseline to week 24 in the visual-analogue scale (VAS) pain score (range, 0 to 100, with higher scores indicating more pain) and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score (range, 0 to 52, with lower scores indicating more fatigue). Safety was also assessed. RESULTS: A total of 83 patients were enrolled, with 41 assigned to the satralizumab group and 42 to the placebo group. The median treatment duration with satralizumab in the double-blind period was 107.4 weeks. Relapse occurred in 8 patients (20%) receiving satralizumab and in 18 (43%) receiving placebo (hazard ratio, 0.38; 95% confidence interval [CI], 0.16 to 0.88). Multiple imputation for censored data resulted in hazard ratios ranging from 0.34 to 0.44 (with corresponding P values of 0.01 to 0.04). Among 55 AQP4-IgG-seropositive patients, relapse occurred in 11% of those in the satralizumab group and in 43% of those in the placebo group (hazard ratio, 0.21; 95% CI, 0.06 to 0.75); among 28 AQP4-IgG-seronegative patients, relapse occurred in 36% and 43%, respectively (hazard ratio, 0.66; 95% CI, 0.20 to 2.24). The between-group difference in the change in the mean VAS pain score was 4.08 (95% CI, -8.44 to 16.61); the between-group difference in the change in the mean FACIT-F score was -3.10 (95% CI, -8.38 to 2.18). The rates of serious adverse events and infections did not differ between groups. CONCLUSIONS: Among patients with NMOSD, satralizumab added to immunosuppressant treatment led to a lower risk of relapse than placebo but did not differ from placebo in its effect on pain or fatigue. (Funded by Chugai Pharmaceutical; ClinicalTrials.gov number, NCT02028884.).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Neuromielite Óptica/tratamento farmacológico , Receptores de Interleucina-6/antagonistas & inibidores , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Aquaporina 4/imunologia , Autoanticorpos/sangue , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Imunoglobulina G/sangue , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neuromielite Óptica/imunologia , Receptores de Interleucina-6/imunologia , Recidiva , Adulto Jovem
3.
Rinsho Shinkeigaku ; 59(11): 736-739, 2019 Nov 08.
Artigo em Japonês | MEDLINE | ID: mdl-31656264

RESUMO

A 20-year-old woman was hospitalized after experiencing headaches, high fever, and nausea for 1 week. She was conscious and had no abnormal neurological findings or neck stiffness. Examination of her cerebrospinal fluid showed a pronounced elevation of mononuclear cells. She was admitted to our hospital with the diagnosis of meningitis and had hypersomnia 3 days later. Brain MRI (FLAIR) demonstrated high-intensity lesions at the dorsal pons, and bilateral hypothalamus and spinal MRI demonstrated longitudinal T2 high-intensity lesions extending from C2 to C4 and from C6 to Th6. We suspected neuromyelitis optica spectrum disorder (NMOSD) and administered intravenous methylprednisolone after which her symptoms and MRI abnormalities improved immediately. Serum anti-aquaporin-4 antibody and anti-myelin oligodendrocyte glycoprotein antibody were negative. Thus, it is important to perform MRI imaging early in the onset of aseptic meningitis due to numerous case reports of patients diagnosed with neuromyelitis optica or NMOSD with initial meningitis-like symptoms.


Assuntos
Meningite Asséptica , Neuromielite Óptica/diagnóstico , Adulto , Encéfalo/diagnóstico por imagem , Diagnóstico Diferencial , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Meningite Asséptica/diagnóstico , Metilprednisolona/administração & dosagem , Neuromielite Óptica/tratamento farmacológico , Pulsoterapia , Medula Espinal/diagnóstico por imagem , Resultado do Tratamento , Adulto Jovem
4.
BMC Neurol ; 19(1): 234, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31607267

RESUMO

BACKGROUND: This article reports a case diagnosis of a 44-year-old female who presented with intractable hiccups and vomit complicated with an acute onset of paraplegia. Transverse myelitis was evident on MRI and serological studies were consistent with Neuromyelitis Optica (NMO) based on NMO-IgG sero-positivity. Further studies revealed positive ANA, anti-RNA polymerase III autoantibodies, and Scl-70, leading to a concurrent diagnosis of systemic sclerosis (SSc). The coexistence of these two disease processes and their underlying clinical manifestations and therapeutic interventions are seldom reported in literature and are worth reporting. CASE PRESENTATION: The patient was treated with high dose steroids, and subsequently developed malignant hypertension and acute renal failure, later identified on biopsy as steroids-induced scleroderma renal crisis. Although Neuromyelitis Optica spectrum disorder (NMOSD) has often been associated with various collagen and autoimmune diseases, the coexistence of NMOSD and SSc presented a challenge where the patient underwent aggressive physical therapy and necessitated an intervention with Rituximab to achieve an appropriate clinical response. We have received a written consent forms from the participant in our study, and we have them on file in case they are requested. We have also received the patient's written consent for the data and images presented in this article. CONCLUSION: This article expands on NMOSD associated autoimmune diseases. Systemic Sclerosis is an insidious disease that is often diagnosed late as not all patients often report skin manifestation. The finding suggests that patients presenting with acute neurological manifestations get tested for NMO-IgG/AQP-4 antibodies and other immunological studies based on clinical findings.


Assuntos
Mielite Transversa/etiologia , Neuromielite Óptica/complicações , Escleroderma Sistêmico/complicações , Adulto , Autoanticorpos/sangue , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Imagem por Ressonância Magnética , Mielite Transversa/tratamento farmacológico , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/tratamento farmacológico , Rituximab/uso terapêutico , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/tratamento farmacológico , Síndrome
5.
Medicina (B Aires) ; 79 Suppl 3: 60-65, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31603846

RESUMO

Neuromyelitis optica (NMO) is an autoimmune, inflammatory and de myelinat ing disorder of the central nervous system with a predilection for the optic nerves and spinal cord. In 2004 the association of NMO with an antibody against the water channel aquaporin 4 (anti-AQP4) was published as a different pathology from multiple sclerosis (MS). Currently the term NMO spectrum disorders (NMOSD) is proposed, because the manifestations of the disease can be more extensive, affecting in addition to the optic nerve and spinal cord, the area postrema of the dorsal medulla, brainstem, diencephalon and typical brain areas (periependymal, corpus callosum, internal capsule and subcortical white matter). NMOSD is also applied to patients who meet the NMO criteria and are negative for AQP4-IgG. Within the latter group, the presence of another antibody, anti-MOG, has been detected in 20%, with a different physiopathological mechanism, but with a similar clinic and a better prognosis. The immunosuppressive treatment in the attack, as well as the long-term treatment in the cases that are indicated, is fundamental to avoid sequelaes and recurrences. The correct diagnosis of this entity is essential since it can be aggravated with the use of drugs useful in the treatment of MS. In this publication we will review the pathophysiology, clinical and diagnostic criteria of NMOSD, and discuss the different therapeutic options.


Assuntos
Autoanticorpos/imunologia , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/tratamento farmacológico , Autoanticorpos/efeitos adversos , Diagnóstico Diferencial , Humanos , Esclerose Múltipla/diagnóstico , Neuromielite Óptica/imunologia , Neuromielite Óptica/fisiopatologia
6.
Lancet ; 394(10206): 1352-1363, 2019 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-31495497

RESUMO

BACKGROUND: No approved therapies exist for neuromyelitis optica spectrum disorder (NMOSD), a rare, relapsing, autoimmune, inflammatory disease of the CNS that causes blindness and paralysis. We aimed to assess the efficacy and safety of inebilizumab, an anti-CD19, B cell-depleting antibody, in reducing the risk of attacks and disability in NMOSD. METHODS: We did a multicentre, double-blind, randomised placebo-controlled phase 2/3 study at 99 outpatient specialty clinics or hospitals in 25 countries. Eligible participants were adults (≥18 years old) with a diagnosis of NMOSD, an Expanded Disability Status Scale score of 8·0 or less, and a history of at least one attack requiring rescue therapy in the year before screening or at least two attacks requiring rescue therapy in the 2 years before screening. Participants were randomly allocated (3:1) to 300 mg intravenous inebilizumab or placebo with a central interactive voice response system or interactive web response system and permuted block randomisation. Inebilizumab or placebo was administered on days 1 and 15. Participants, investigators, and all clinical staff were masked to the treatments, and inebilizumab and placebo were indistinguishable in appearance. The primary endpoint was time to onset of an NMOSD attack, as determined by the adjudication committee. Efficacy endpoints were assessed in all randomly allocated patients who received at least one dose of study intervention, and safety endpoints were assessed in the as-treated population. The study is registered with ClinicalTrials.gov, number NCT02200770. FINDINGS: Between Jan 6, 2015, and Sept 24, 2018, 230 participants were randomly assigned to treatment and dosed, with 174 participants receiving inebilizumab and 56 receiving placebo. The randomised controlled period was stopped before complete enrolment, as recommended by the independent data-monitoring committee, because of a clear demonstration of efficacy. 21 (12%) of 174 participants receiving inebilizumab had an attack versus 22 (39%) of 56 participants receiving placebo (hazard ratio 0·272 [95% CI 0·150-0·496]; p<0·0001). Adverse events occurred in 125 (72%) of 174 participants receiving inebilizumab and 41 (73%) of 56 participants receiving placebo. Serious adverse events occurred in eight (5%) of 174 participants receiving inebilizumab and five (9%) of 56 participants receiving placebo. INTERPRETATION: Compared with placebo, inebilizumab reduced the risk of an NMOSD attack. Inebilizumab has potential application as an evidence-based treatment for patients with NMOSD. FUNDING: MedImmune and Viela Bio.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Neuromielite Óptica/tratamento farmacológico , Adolescente , Adulto , Idoso , Método Duplo-Cego , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Neuromielite Óptica/complicações , Estudos Prospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
7.
Medicine (Baltimore) ; 98(34): e16906, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441871

RESUMO

RATIONALE: Brain abnormalities have frequently been reported in neuromyelitis optica spectrum disorders patients, but vertigo as an initial manifestation has rarely been described. PATIENT CONCERNS: A 64-year-old woman who initially presented with vertigo, then accompanied with other brainstem manifestations and spinal cord involvement. DIAGNOSES: MRI revealed medulla oblongata, cervical and thoracic spinal cord lesions. NMO-IgG antibody was seropositive. Taken her previous medical history and clinical manifestations into consideration, the patient was eventually diagnosed as neuromyelitis optica spectrum disorders. INTERVENTIONS: Before diagnosis, symptomatic treatment and acupuncture were adopted, whereas after diagnosis, steroid, intravenous immunoglobulin, and immunosuppressant were supplemented. OUTCOMES: Her dizziness, nausea and vomiting were gradually relieved by symptomatic treatment and acupuncture before the confirmed diagnosis and immunotherapy. After added treatment with steroid, immunosuppressant, especially intravenous immunoglobulin, diplopia and nystagmus disappeared, and superficial sensation was improving. She was fully recovered six months after admission. LESSONS: Vertigo as a rare prodrome of neuromyelitis optica spectrum disorders deserves attention. The symptoms and signs were improved by a combined treatment of steroid, immunosuppressant, acupuncture, and particularly intravenous immunoglobulin.


Assuntos
Neuromielite Óptica/diagnóstico , Vertigem/etiologia , Terapia por Acupuntura , Diplopia/etiologia , Diplopia/terapia , Feminino , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Fatores Imunológicos/administração & dosagem , Pessoa de Meia-Idade , Náusea/etiologia , Náusea/terapia , Neuromielite Óptica/tratamento farmacológico , Vértebras Torácicas/diagnóstico por imagem , Vertigem/terapia , Vômito/etiologia , Vômito/terapia
8.
J Neuroinflammation ; 16(1): 134, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266527

RESUMO

BACKGROUND: Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) are related to several acquired demyelinating syndromes in adults, but the therapeutic approach is currently unclear. We aimed to describe the response to different therapeutic strategies in adult patients with relapsing MOG-Ab-associated disease. METHODS: This is a retrospective study conducted in France and Spain including 125 relapsing MOG-Ab patients aged ≥ 18 years. First, we performed a survival analysis to investigate the relapse risk between treated and non-treated patients, performing a propensity score method based on the inverse probability of treatment weighting. Second, we assessed the annualised relapse rates (ARR), Expanded Disability Status Scale (EDSS) and visual acuity pre-treatment and on/end-treatment. RESULTS: Median age at onset was 34.1 years (range 18.0-67.1), the female to male ratio was 1.2:1, and 96% were Caucasian. At 5 years, 84% (95% confidence interval [CI], 77.1-89.8) patients relapsed. At the last follow-up, 66 (52.8%) received maintenance therapy. Patients initiating immunosuppressants (azathioprine, mycophenolate mophetil [MMF], rituximab) were at lower risk of new relapse in comparison to non-treated patients (HR, 0.41; 95CI%, 0.20-0.82; p = 0.011). Mean ARR (standard deviation) was reduced from 1.05(1.20) to 0.43(0.79) with azathioprine (n = 11; p = 0.041), from 1.20(1.11) to 0.23(0.60) with MMF (n = 11; p = 0.033), and from 1.08(0.98) to 0.43(0.89) with rituximab (n = 26; p = 0.012). Other immunosuppressants (methotrexate/mitoxantrone/cyclophosphamide; n = 5), or multiple sclerosis disease-modifying drugs (MS-DMD; n = 9), were not associated with significantly reduced ARR. Higher rates of freedom of EDSS progression were observed with azathioprine, MMF or rituximab. CONCLUSION: In adults with relapsing MOG-Ab-associated disease, immunosuppressant therapy (azathioprine, MMF and rituximab) is associated with reduced risk of relapse and better disability outcomes. Such an effect was not found in the few patients treated with MS-DMD.


Assuntos
Autoanticorpos/sangue , Imunossupressores/uso terapêutico , Glicoproteína Mielina-Oligodendrócito/sangue , Neuromielite Óptica/sangue , Neuromielite Óptica/tratamento farmacológico , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/sangue , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Neuromielite Óptica/diagnóstico , Estudos Retrospectivos , Rituximab/uso terapêutico , Resultado do Tratamento , Adulto Jovem
10.
Intern Med ; 58(22): 3319-3321, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31327827

RESUMO

Antibody against myelin oligodendrocyte glycoprotein (MOG-IgG) associated encephalitis is an important syndrome associated with MOG-IgG. However, there have been no reports of MOG-IgG-associated optic neuritis or demyelination following meningitis without encephalitic symptoms. A 55-year-old woman presented to our hospital with headache, nausea, fever, and nuchal rigidity that had persisted for more than a month. She was hospitalized due to aseptic meningitis and recovered with conservative therapy. However, she was re-admitted due to left optic neuritis and demyelinating lesions. We diagnosed MOG-IgG-associated neuromyelitis optica spectrum disorder (NMOSD). She responded to treatment with intravenous methylprednisolone and oral prednisolone. Aseptic meningitis may be an initial manifestation of MOG-IgG-positive NMOSD.


Assuntos
Meningite Asséptica/complicações , Neuromielite Óptica/complicações , Corticosteroides/uso terapêutico , Autoanticorpos , Feminino , Humanos , Pessoa de Meia-Idade , Glicoproteína Mielina-Oligodendrócito/imunologia , Neuromielite Óptica/tratamento farmacológico
11.
Medicine (Baltimore) ; 98(25): e15944, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31232925

RESUMO

OBJECTIVE: To test the safety of ublituximab, a B cell depleting agent, as add-on therapy in the acute treatment of relapses of neuromyelitis optica spectrum disorder. METHODS: We conducted an open-label phase 1b safety and proof-of-concept trial in 5 subjects with aquaporin-4 (AQP4)-immunoglobulin G (IgG) seropositive neuromyelitis optica spectrum disorder (NMOSD) who presented with acute transverse myelitis and/or optic neuritis. In addition to treating with 1 g of daily intravenous methylprednisolone, we infused a single dose of 450 mg of ublituximab within 5 days of relapse onset. The primary outcome measure was safety, and the secondary efficacy measures included change in Expanded Disability Status Scale (EDSS), durability of remission and B cell counts. RESULTS: Five NMOSD subjects were enrolled, 4 of whom presented with acute transverse myelitis and 1 with acute optic neuritis. Ublituximab proved to be safe in all 5 NMOSD subjects, with no serious adverse events recorded. There were no opportunistic infections in any of the subjects; however, 1 subject experienced a transient leukopenia. EDSS scores dropped from a median of 6.5 on admission to 4.0 on 90-day follow up. Two subjects did not achieve total B cell depletion and relapsed within 3 months. CONCLUSIONS: Ublituximab is a safe add-on therapy for NMOSD patients presenting with acute transverse myelitis and optic neuritis. Preliminary evidence suggests a promising benefit on durability of remission when B cell depletion is achieved. A placebo-controlled trial is necessary to confirm these findings. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with NMOSD with acute transverse myelitis or optic neuritis, ublituximab is safe and may improve neurological outcome.


Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Antígenos CD20 , Metilprednisolona/uso terapêutico , Neuromielite Óptica/tratamento farmacológico , Anti-Inflamatórios/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Masculino , Metilprednisolona/administração & dosagem , Neuromielite Óptica/patologia , Projetos Piloto , Recidiva , Resultado do Tratamento
12.
Neurology ; 93(2): e181-e189, 2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31171648

RESUMO

OBJECTIVE: To report the yearly incidence rate and prevalence of neuromyelitis spectrum disorder (NMOSD) in Sweden and to investigate clinical characteristics, treatment, and outcome. METHODS: We conducted a retrospective study of hospital case records of 294 individuals diagnosed with neuromyelitis optica (NMO) (G36.0 ICD-10, 341.0 ICD-9) in the Swedish National Patient Register from 1987 to end of 2013 or detected by the presence of aquaporin-4 (AQP4) immunoglobulin G (IgG) in serum during the study period. Ninety-two patients (51 NMO and 41 NMOSD) met the 2006 Wingerchuk criteria and were included in the study. Ten patients with an onset of NMO prior to 1987 and alive at the end of 2013 were included when estimating the prevalence. RESULTS: The average yearly incidence rate per 1,000,000 individuals increased significantly from 0.30 (confidence interval [CI] 0.19-0.41) between 1987 and 2006 to 0.79 (CI 0.55-1.03) between 2007 and 2013. The prevalence was 10.4 (CI 8.5-12.6) per 1,000,000 individuals at end of 2013. The median time from onset to first relapse was 1.42 years (range 0.58-3.90). The probability of relapse was 60% and 75% after 5 and 10 years after onset. More than 80% were treated with immunosuppressive drugs. Three patients died during the study period. CONCLUSION: The increased incidence rate during the study period was likely due to heightened awareness and increased access to MRI and AQP4-IgG analysis. Incidence and prevalence of NMO in Sweden correspond to other countries with a predominately Caucasian population. We found that most patients were treated with immunosuppressant drugs, presumably resulting in low mortality among the detected cases.


Assuntos
Neuromielite Óptica/epidemiologia , Corticosteroides/uso terapêutico , Adulto , Azatioprina/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Neuromielite Óptica/tratamento farmacológico , Prevalência , Rituximab/uso terapêutico , Suécia/epidemiologia
13.
Brain Nerve ; 71(6): 573-580, 2019 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-31171754

RESUMO

Neuromyelitis optica (NMO) is clinically characterized by severe optic neuritis and long myelitis; and is associated with aquaporin-4 immunoglobulin-G (AQP4-IgG), an autoantibody directed against aquaporin-4 (AQP4), which is an astrocytic water channel protein. Until recent years, the treatment of NMO has mainly focused on the suppression of lymphocytes and depletion of autoantibodies. However, several studies on the pathogehesis of the disease in human pathology, cultured cells, and animal models have revealed that astrocyte injury in NMO is mainly caused by the complement-dependent cytotoxicity following AQP4-IgG binding to AQP4. Moreover, complement-targeting therapy has recently been translated into practical applications in several hematological disorders. and similary, also in the cases of NMO. In this article, we review the relevance of the complement system in the pathogenesis of NMO. Additionally, we review the current status and prospects of the complement-targeting therapy for NMO, including the clinical trials of eculizumab and C1 inhibitor for NMO, and the experimental studies on C1 inhibition by monoclonal antibodies.


Assuntos
Aquaporina 4/imunologia , Inativadores do Complemento/uso terapêutico , Proteínas do Sistema Complemento , Neuromielite Óptica/tratamento farmacológico , Neuromielite Óptica/patologia , Animais , Anticorpos Monoclonais Humanizados/uso terapêutico , Autoanticorpos , Ensaios Clínicos como Assunto , Complemento C1/antagonistas & inibidores , Humanos , Imunoglobulina G
14.
Continuum (Minneap Minn) ; 25(3): 753-772, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31162315

RESUMO

PURPOSE OF REVIEW: This article discusses the prevalence, identification, and management of multiple sclerosis (MS)-related symptoms and associated comorbidities, including complications that can present at all stages of the disease course. RECENT FINDINGS: The impact of comorbidities on the outcome of MS is increasingly recognized. This presents an opportunity to impact the course and outcome of MS by identifying and treating associated comorbidities that may be more amenable to treatment than the underlying inflammatory and neurodegenerative disease. The identification of MS-related symptoms and comorbidities is facilitated by brief screening tools, ideally completed by the patient and automatically entered into the patient record, with therapeutic suggestions for the provider. The development of free, open-source screening tools that can be integrated with electronic health records provides opportunities to identify and treat MS-related symptoms and comorbidities at an early stage. SUMMARY: Identification and management of MS-related symptoms and comorbidities can lead to improved outcomes, improved quality of life, and reduced disease activity. The use of brief patient-reported screening tools at or before the point of care can facilitate identification of symptoms and comorbidities that may be amenable to intervention.


Assuntos
Gerenciamento Clínico , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/tratamento farmacológico , Neuromielite Óptica/diagnóstico por imagem , Neuromielite Óptica/tratamento farmacológico , Anticonvulsivantes/administração & dosagem , Carbamazepina/administração & dosagem , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/epidemiologia , Comorbidade , Depressão/diagnóstico por imagem , Depressão/tratamento farmacológico , Depressão/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Esclerose Múltipla/epidemiologia , Doenças Neurodegenerativas/diagnóstico por imagem , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/epidemiologia , Neuromielite Óptica/epidemiologia
15.
Continuum (Minneap Minn) ; 25(3): 793-814, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31162317

RESUMO

PURPOSE OF REVIEW: This article provides an up-to-date summary of the categories, diagnosis, and management of pediatric demyelinating disorders. RECENT FINDINGS: Understanding of the diverse spectrum of pediatric demyelinating disorders, including monophasic and multiphasic forms, has improved. Pediatric multiple sclerosis (MS) is the most common demyelinating disorder in children, and recent genetic and environmental risk research has clarified that pediatric MS is on the same continuum of disease as adult MS. Recent advances in the treatment of pediatric MS include clinical trials leading to regulatory agency-approved treatments. The identification of myelin oligodendrocyte glycoprotein and aquaporin-4 antibodies in children has been a major advance, allowing for appropriate treatment and management of these syndromes. SUMMARY: Antibody testing is now helping to define subtypes of pediatric demyelinating disorders, including myelin oligodendrocyte glycoprotein-seropositive and aquaporin-4-seropositive cases that are distinct from pediatric MS. Treatments for pediatric MS are being evaluated in clinical trials.


Assuntos
Aquaporina 4/líquido cefalorraquidiano , Glicoproteína Mielina-Oligodendrócito/líquido cefalorraquidiano , Neuromielite Óptica/líquido cefalorraquidiano , Neuromielite Óptica/diagnóstico por imagem , Adolescente , Criança , Doenças Desmielinizantes/líquido cefalorraquidiano , Doenças Desmielinizantes/diagnóstico por imagem , Doenças Desmielinizantes/tratamento farmacológico , Encefalomielite/líquido cefalorraquidiano , Encefalomielite/diagnóstico por imagem , Encefalomielite/tratamento farmacológico , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Ácido Micofenólico/administração & dosagem , Neuromielite Óptica/tratamento farmacológico
16.
Mult Scler Relat Disord ; 33: 22-32, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31136907

RESUMO

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory and autoimmune disorder of the central nervous system that typically presents with optic neuritis and myelitis. Azathioprine (AZA) is one of the available immunotherapies with purported beneficial effects for patients with NMOSD. At present, there are no systematic reviews that extensively pooled the effects of AZA compared to other interventions for this condition. The objective of this study, therefore, is to determine the efficacy and safety of AZA in patients with NMOSD using systematic review of relevant studies. METHODS: Major health electronic databases, which included CENTRAL, MEDLINE, EMBASE, Scopus, LILACS, ClinicalTrials.gov, and HERDIN, were searched from May 2017 to November 2018 for relevant studies involving adult and pediatric patients with NMOSD. Randomized controlled trials, and either prospective or retrospective cohort designs that assessed the reduction or prevention of relapse or disability and the occurrence of adverse events related to AZA use compared to placebo or to other active drugs were considered. Assessment of risk of bias was performed using the Cochrane Collaboration tool and Newcastle-Ottawa Scale. RESULTS: From a total of 273 records, 9 relevant studies (1 randomized controlled trial (RCT), 3 prospective cohort studies, 5 retrospective studies) which involved a total of 977 patients, were included. One RCT and several observational studies revealed that AZA regimen may be inferior to rituximab in terms of annualized relapse rate, reduction of disability as measured by the expanded disability status scale (EDSS), risk for relapse and relapse-free rate. Efficacy data were very limited in the comparison of AZA to mycophenolate mofetil (MMF), to cyclophosphamide, and to interferon-ß for patients with NMOSD. Occurrence of any adverse event, elevated liver enzymes/hepatoxicity, leukopenia and hair loss associated with AZA use were significantly greater compared to MMF, which may lead to medication noncompliance. CONCLUSION: AZA improves relapses and disability in patients with NMOSD but this regimen is associated with relatively frequent adverse events based on limited published evidences. More well-conducted clinical trials are necessary to establish with certainty the beneficial and harmful effects of AZA in patients with NMOSD.


Assuntos
Azatioprina/uso terapêutico , Imunossupressores/uso terapêutico , Neuromielite Óptica/tratamento farmacológico , Humanos
17.
N Engl J Med ; 381(7): 614-625, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31050279

RESUMO

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing, autoimmune, inflammatory disorder that typically affects the optic nerves and spinal cord. At least two thirds of cases are associated with aquaporin-4 antibodies (AQP4-IgG) and complement-mediated damage to the central nervous system. In a previous small, open-label study involving patients with AQP4-IgG-positive disease, eculizumab, a terminal complement inhibitor, was shown to reduce the frequency of relapse. METHODS: In this randomized, double-blind, time-to-event trial, 143 adults were randomly assigned in a 2:1 ratio to receive either intravenous eculizumab (at a dose of 900 mg weekly for the first four doses starting on day 1, followed by 1200 mg every 2 weeks starting at week 4) or matched placebo. The continued use of stable-dose immunosuppressive therapy was permitted. The primary end point was the first adjudicated relapse. Secondary outcomes included the adjudicated annualized relapse rate, quality-of-life measures, and the score on the Expanded Disability Status Scale (EDSS), which ranges from 0 (no disability) to 10 (death). RESULTS: The trial was stopped after 23 of the 24 prespecified adjudicated relapses, given the uncertainty in estimating when the final event would occur. The mean (±SD) annualized relapse rate in the 24 months before enrollment was 1.99±0.94; 76% of the patients continued to receive their previous immunosuppressive therapy during the trial. Adjudicated relapses occurred in 3 of 96 patients (3%) in the eculizumab group and 20 of 47 (43%) in the placebo group (hazard ratio, 0.06; 95% confidence interval [CI], 0.02 to 0.20; P<0.001). The adjudicated annualized relapse rate was 0.02 in the eculizumab group and 0.35 in the placebo group (rate ratio, 0.04; 95% CI, 0.01 to 0.15; P<0.001). The mean change in the EDSS score was -0.18 in the eculizumab group and 0.12 in the placebo group (least-squares mean difference, -0.29; 95% CI, -0.59 to 0.01). Upper respiratory tract infections and headaches were more common in the eculizumab group. There was one death from pulmonary empyema in the eculizumab group. CONCLUSIONS: Among patients with AQP4-IgG-positive NMOSD, those who received eculizumab had a significantly lower risk of relapse than those who received placebo. There was no significant between-group difference in measures of disability progression. (Funded by Alexion Pharmaceuticals; PREVENT ClinicalTrials.gov number, NCT01892345; EudraCT number, 2013-001150-10.).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Aquaporina 4/imunologia , Complemento C5/antagonistas & inibidores , Inativadores do Complemento/uso terapêutico , Imunossupressores/uso terapêutico , Neuromielite Óptica/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Autoanticorpos/sangue , Inativadores do Complemento/efeitos adversos , Avaliação da Deficiência , Progressão da Doença , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Cefaleia/induzido quimicamente , Humanos , Imunoglobulina G/sangue , Imunossupressores/efeitos adversos , Masculino , Neuromielite Óptica/imunologia , Qualidade de Vida , Infecções Respiratórias/etiologia , Prevenção Secundária
18.
Mult Scler Relat Disord ; 32: 27-29, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31026608

RESUMO

Treatment of MOG Ab-associated disease is poorly standardized: several drugs have been employed, with variable results. A 50-year-old Caucasian male was admitted to hospital in 2009, with severe acute transverse myelitis. A brain and spinal cord MRI showed multiple demyelinating lesions and cerebrospinal fluid analysis revealed no oligoclonal bands (OCBs). A diagnosis of multiple sclerosis (MS) was made. He was treated with interferon-beta 1a, then with fingolimod, and finally with rituximab. All these treatments were ineffective: he experienced several spinal and brainstem relapses, with residual disability. Finally, an empirical therapy with IVIg was started. Calling into question the diagnosis of MS, we performed anti-MOG test (positive). IVIg therapy was continued and the patient experienced only one mild relapse during a 24-month follow-up. Our patient, with an aggressive and atypical MOG Ab-associated disease, showed a very good response to longterm IVIg treatment.


Assuntos
Imunoglobulinas Intravenosas/administração & dosagem , Glicoproteína Mielina-Oligodendrócito , Neuromielite Óptica/diagnóstico por imagem , Neuromielite Óptica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Glicoproteína Mielina-Oligodendrócito/sangue , Neuromielite Óptica/sangue , Resultado do Tratamento
19.
J Coll Physicians Surg Pak ; 29(4): 379-380, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30925966

RESUMO

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune relapsing demyelinating disorder which often leads to severe disability typically targeting spinal cord, optic nerves, and brainstem. Around 75% of NMOSD patients have serum immunoglobulin-G (IgG) autoantibodies to the aquaporin-4 channel (AQP4-IgG). AQP4-IgG antibodies have a central role in new diagnostic criteria of NMOSD. These antibodies have a critical role in long-term management after the first attack. The prevalence of this disorder is lower than multiple sclerosis in European countries. However, NMO makes a substantial proportion of the demyelinating diseases of the central nervous system in countries like Pakistan, where it can be mistaken for multiple sclerosis. Accurate diagnosis is essential as some of the drugs for multiple sclerosis can potentially worsen NMOSD. We present a case of sequential optic neuritis with positive aquaporin 4 antibodies. We have discussed the history, examination findings, diagnostic workups, and treatment of the patient.


Assuntos
Aquaporina 4/sangue , Autoanticorpos/sangue , Neuromielite Óptica/diagnóstico , Neurite Óptica/diagnóstico , Adolescente , Azatioprina/administração & dosagem , Feminino , Humanos , Imunoglobulina G/sangue , Neuromielite Óptica/sangue , Neuromielite Óptica/tratamento farmacológico , Neuromielite Óptica/terapia , Neurite Óptica/sangue , Neurite Óptica/terapia , Troca Plasmática/métodos , Prednisolona/administração & dosagem , Resultado do Tratamento
20.
Neuropediatrics ; 50(3): 193-196, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30913570

RESUMO

B cell depletion with the anti-CD20-antibody rituximab is widely considered treatment of choice for long-term immunotherapy in aquaporin-4 (AQP4)-antibody positive neuromyelitis optica spectrum disorder (NMOSD). However, up to 30% of patients suffer from relapses despite complete B cell depletion. In these cases, the IL6 (interleukin-6)-receptor blocking antibody tocilizumab has been suggested as an alternative. We report two female adolescents with AQP4-antibody positive NMOSD who relapsed under rituximab treatment and clinically stabilized after switching to monthly administrations of tocilizumab. Our data suggest that early escalation of therapy with tocilizumab may lead to stabilization of disease activity in pediatric NMOSD patients who relapse under B cell depletion.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Aquaporina 4/sangue , Autoanticorpos/sangue , Neuromielite Óptica/sangue , Neuromielite Óptica/tratamento farmacológico , Adolescente , Feminino , Humanos , Neuromielite Óptica/diagnóstico por imagem , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA