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  • 1
    Online Resource
    Online Resource
    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
    Springer Science and Business Media LLC ; 2023
    In:  Journal of Neurology
    Details
    In: Journal of Neurology, Springer Science and Business Media LLC
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0340-5354 , 1432-1459
    URL: Article
    DOI: 10.1007/s00415-023-11910-z
    RVK:
    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 1421299-7
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  • 2
    Online Resource
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    Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity
    Proceedings of the National Academy of Sciences ; 2021
    In:  Proceedings of the National Academy of Sciences Vol. 118, No. 1 ( 2021-01-05)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 118, No. 1 ( 2021-01-05)
    Abstract: Multiple sclerosis (MS) disease risk is associated with reduced sun-exposure. This study assessed the relationship between measures of sun exposure (vitamin D [vitD], latitude) and MS severity in the setting of two multicenter cohort studies ( n NationMS = 946, n BIONAT = 990). Additionally, effect-modification by medication and photosensitivity-associated MC1R variants was assessed. High serum vitD was associated with a reduced MS severity score (MSSS), reduced risk for relapses, and lower disability accumulation over time. Low latitude was associated with higher vitD, lower MSSS, fewer gadolinium-enhancing lesions, and lower disability accumulation. The association of latitude with disability was lacking in IFN-β–treated patients. In carriers of MC1R :rs1805008(T), who reported increased sensitivity toward sunlight, lower latitude was associated with higher MRI activity, whereas for noncarriers there was less MRI activity at lower latitudes. In a further exploratory approach, the effect of ultraviolet (UV)-phototherapy on the transcriptome of immune cells of MS patients was assessed using samples from an earlier study. Phototherapy induced a vitD and type I IFN signature that was most apparent in monocytes but that could also be detected in B and T cells. In summary, our study suggests beneficial effects of sun exposure on established MS, as demonstrated by a correlative network between the three factors: Latitude, vitD, and disease severity. However, sun exposure might be detrimental for photosensitive patients. Furthermore, a direct induction of type I IFNs through sun exposure could be another mechanism of UV-mediated immune-modulation in MS.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2018457118
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2021
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 3
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    Neuromyelitis optica: Evaluation of 871 attacks and 1,153 treatment courses
    Wiley ; 2016
    In:  Annals of Neurology Vol. 79, No. 2 ( 2016-02), p. 206-216
    Details
    In: Annals of Neurology, Wiley, Vol. 79, No. 2 ( 2016-02), p. 206-216
    Abstract: Neuromyelitis optica (NMO) attacks often are severe, are difficult to treat, and leave residual deficits. Here, we analyzed the frequency, sequence, and efficacy of therapies used for NMO attacks. Methods A retrospective review was made of patient records to assess demographic/diagnostic data, attack characteristics, therapies, and the short‐term remission status (complete remission [CR], partial remission [PR] , no remission [NR]). Inclusion criteria were NMO according to Wingerchuk's 2006 criteria or aquaporin‐4 antibody–positive NMO spectrum disorder (NMOSD). Remission status was analyzed with generalized estimating equations (GEEs), a patient‐based statistical approach. Results A total of 871 attacks in 185 patients (142 NMO/43 NMOSD, 82% female) were analyzed. The 1,153 treatment courses comprised high‐dose intravenous steroids (HD‐S; n = 810), plasma exchange (PE; n = 192), immunoadsorption (IA; n = 38), other (n = 80), and unknown (n = 33) therapies. The first treatment course led to CR in 19.1%, PR in 64.5%, and NR in 16.4% of attacks. Second, third, fourth, and fifth treatment courses were given in 28.2%, 7.1%, 1.4%, and 0.5% of attacks, respectively. This escalation of attack therapy significantly improved outcome ( p   〈  0.001, Bowker test). Remission rates were higher for isolated optic neuritis versus isolated myelitis ( p   〈  0.001), and for unilateral versus bilateral optic neuritis ( p  = 0.020). Isolated myelitis responded better to PE/IA than to HD‐S as first treatment course ( p  = 0.037). Predictors of CR in multivariate GEE analysis were age (odds ratio [OR] = 0.97, p  = 0.011), presence of myelitis (OR = 0.38, p  = 0.002), CR from previous attack (OR = 6.85, p   〈  0.001), and first‐line PE/IA versus HD‐S (OR = 4.38, p  = 0.006). Interpretation Particularly myelitis and bilateral optic neuritis have poor remission rates. Escalation of attack therapy improves outcome. PE/IA may increase recovery in isolated myelitis. Ann Neurol 2016;79:206–216
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    URL: Article
    DOI: 10.1002/ana.v79.2
    DOI: 10.1002/ana.24554
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 2037912-2
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  • 4
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    Apheresis therapies for NMOSD attacks : A retrospective study of 207 therapeutic interventions
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Neurology - Neuroimmunology Neuroinflammation Vol. 5, No. 6 ( 2018-11), p. e504-
    Details
    In: Neurology - Neuroimmunology Neuroinflammation, Ovid Technologies (Wolters Kluwer Health), Vol. 5, No. 6 ( 2018-11), p. e504-
    Abstract: To analyze whether 1 of the 2 apheresis techniques, therapeutic plasma exchange (PE) or immunoadsorption (IA), is superior in treating neuromyelitis optica spectrum disorder (NMOSD) attacks and to identify predictive factors for complete remission (CR). Methods This retrospective cohort study was based on the registry of the German Neuromyelitis Optica Study Group, a nationwide network established in 2008. It recruited patients with neuromyelitis optica diagnosed according to the 2006 Wingerchuk criteria or with aquaporin-4 (AQP4-ab)-antibody–seropositive NMOSD treated at 6 regional hospitals and 16 tertiary referral centers until March 2013. Besides descriptive data analysis of patient and attack characteristics, generalized estimation equation (GEE) analyses were applied to compare the effectiveness of the 2 apheresis techniques. A GEE model was generated to assess predictors of outcome. Results Two hundred and seven attacks in 105 patients (87% AQP4-ab-antibody seropositive) were treated with at least 1 apheresis therapy. Neither PE nor IA was proven superior in the therapy of NMOSD attacks. CR was only achieved with early apheresis therapy. Strong predictors for CR were the use of apheresis therapy as first-line therapy (OR 12.27, 95% CI: 1.04–144.91, p = 0.047), time from onset of attack to start of therapy in days (OR 0.94, 95% CI: 0.89–0.99, p = 0.014), the presence of AQP4-ab-antibodies (OR 33.34, 95% CI: 1.76–631.17, p = 0.019), and monofocal attack manifestation (OR 4.71, 95% CI: 1.03–21.62, p = 0.046). Conclusions Our findings suggest early use of an apheresis therapy in NMOSD attacks, particularly in AQP4-ab-seropositive patients. No superiority was shown for one of the 2 apheresis techniques. Classification of evidence This study provides Class IV evidence that for patients with NMOSD, neither PE nor IA is superior in the treatment of attacks.
    Type of Medium: Online Resource
    ISSN: 2332-7812
    URL: Article
    DOI: 10.1212/NXI.0000000000000504
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 2767740-0
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  • 5
    Online Resource
    Online Resource
    Interleukin-6 Receptor Blockade in Treatment-Refractory MOG-IgG–Associated Disease and Neuromyelitis Optica Spectrum Disorders
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Neurology - Neuroimmunology Neuroinflammation Vol. 9, No. 1 ( 2022-01), p. e1100-
    Details
    In: Neurology - Neuroimmunology Neuroinflammation, Ovid Technologies (Wolters Kluwer Health), Vol. 9, No. 1 ( 2022-01), p. e1100-
    Abstract: To evaluate the long-term safety and efficacy of tocilizumab (TCZ), a humanized anti–interleukin-6 receptor antibody in myelin oligodendrocyte glycoprotein–IgG–associated disease (MOGAD) and neuromyelitis optica spectrum disorders (NMOSD). Methods Annualized relapse rate (ARR), Expanded Disability Status Scale score, MRI, autoantibody titers, pain, and adverse events were retrospectively evaluated in 57 patients with MOGAD (n = 14), aquaporin-4 (AQP4)-IgG seropositive (n = 36), and seronegative NMOSD (n = 7; 12%), switched to TCZ from previous immunotherapies, particularly rituximab. Results Patients received TCZ for 23.8 months (median; interquartile range 13.0–51.1 months), with an IV dose of 8.0 mg/kg (median; range 6–12 mg/kg) every 31.6 days (mean; range 26–44 days). For MOGAD, the median ARR decreased from 1.75 (range 0.5–5) to 0 (range 0–0.9; p = 0.0011) under TCZ. A similar effect was seen for AQP4-IgG+ (ARR reduction from 1.5 [range 0–5] to 0 [range 0–4.2] ; p 〈 0.001) and for seronegative NMOSD (from 3.0 [range 1.0–3.0] to 0.2 [range 0–2.0] ; p = 0.031). During TCZ, 60% of all patients were relapse free (79% for MOGAD, 56% for AQP4-IgG+, and 43% for seronegative NMOSD). Disability follow-up indicated stabilization. MRI inflammatory activity decreased in MOGAD ( p = 0.04; for the brain) and in AQP4-IgG+ NMOSD ( p 〈 0.001; for the spinal cord). Chronic pain was unchanged. Regarding only patients treated with TCZ for at least 12 months (n = 44), ARR reductions were confirmed, including the subgroups of MOGAD (n = 11) and AQP4-IgG+ patients (n = 28). Similarly, in the group of patients treated with TCZ for at least 12 months, 59% of them were relapse free, with 73% for MOGAD, 57% for AQP4-IgG+, and 40% for patients with seronegative NMOSD. No severe or unexpected safety signals were observed. Add-on therapy showed no advantage compared with TCZ monotherapy. Discussion This study provides Class III evidence that long-term TCZ therapy is safe and reduces relapse probability in MOGAD and AQP4-IgG+ NMOSD.
    Type of Medium: Online Resource
    ISSN: 2332-7812
    URL: Article
    DOI: 10.1212/NXI.0000000000001100
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 6
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    Online Resource
    Aquaporin-4 antibodies in patients treated with natalizumab for suspected MS
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Neurology - Neuroimmunology Neuroinflammation Vol. 4, No. 4 ( 2017-07), p. e363-
    Details
    In: Neurology - Neuroimmunology Neuroinflammation, Ovid Technologies (Wolters Kluwer Health), Vol. 4, No. 4 ( 2017-07), p. e363-
    Abstract: To evaluate (1) the frequency of aquaporin-4 antibody (AQP4-ab)-seropositive cases among patients treated with natalizumab (NAT) and previously diagnosed with MS (MS NAT ) in a nationwide cohort, (2) the clinical course of NAT-treated AQP4-ab–seropositive neuromyelitis optica spectrum disorder (NMOSD) patients (NMO NAT ), (3) AQP4-ab titers in NMO NAT and AQP4-ab–seropositive NMOSD treated with other immunotherapies (NMO IT ), and (4) immune mechanisms influencing disease activity in NMO NAT . Methods: MS NAT serum samples were retrospectively screened with a cell-based assay for AQP4-IgG and titers determined by ELISA. The annualized relapse rate (ARR) and disability progression were assessed. Serum levels of proinflammatory cytokines (interleukin [IL]-1β, IL-4, IL-6, IL-8, IL-10, IL-17, IL-21, and interferon [IFN] -γ) and the chemokine CXCL-10 of NMO NAT patients identified in this (n = 4) and a previous study (n = 5) were measured by cytometric bead array and ELISA. Results: Of the 1,183 MS NAT patients (851 female, median 9 NAT infusions), only 4 (0.33%; 3 female, 1 male) had AQP4-IgG. Of these, 2 fulfilled the 2006 NMO criteria and all met the 2015 NMOSD criteria. The ARR was higher in NMO NAT vs MS NAT ( p = 0.0182). All 4 NMO NAT patients had relapses and 2 had an increase of disability. AQP4-ab titers were higher in NMO NAT (n = 9) vs NMO IT (n = 13; p = 0.0059). IL-8, IL-1β, and IFN-γ serum levels were significantly higher, and CXCL-10 was significantly lower in NMO NAT vs NMO IT . Conclusions: Misdiagnosis of NMOSD with MS is rare. NAT was not able to control disease activity in NMO NAT patients, who had higher serum levels of AQP4-IgG and proinflammatory cytokines than patients with NMOSD treated with other immunotherapies.
    Type of Medium: Online Resource
    ISSN: 2332-7812
    URL: Article
    DOI: 10.1212/NXI.0000000000000363
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 2767740-0
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  • 7
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    Influence of female sex and fertile age on neuromyelitis optica spectrum disorders
    SAGE Publications ; 2017
    In:  Multiple Sclerosis Journal Vol. 23, No. 8 ( 2017-07), p. 1092-1103
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 23, No. 8 ( 2017-07), p. 1092-1103
    Abstract: Gender and age at onset are important epidemiological factors influencing prevalence, clinical presentation, and treatment response in autoimmune diseases. Objective: To evaluate the impact of female sex and fertile age on aquaporin-4-antibody (AQP4-ab) status, attack localization, and response to attack treatment in patients with neuromyelitis optica (NMO) and its spectrum disorders (neuromyelitis optica spectrum disorder (NMOSD)). Methods: Female-to-male ratios, diagnosis at last visit (NMO vs NMOSD), attack localization, attack treatment, and outcome were compared according to sex and age at disease or attack onset. Results: A total of 186 NMO/SD patients (82% female) were included. In AQP4-ab-positive patients, female predominance was most pronounced during fertile age (female-to-male ratio 23:1). Female patients were more likely to be positive for AQP4-abs (92% vs 55%; p  〈  0.001). Interval between onset and diagnosis of NMO/SD was longer in women than in men (mean 54 vs 27 months; p = 0.023). In women, attacks occurring ⩽40 years of age were more likely to show complete remission ( p = 0.003) and better response to high-dose intravenous steroids ( p = 0.005) compared to woman at 〉 40 years. Conclusion: Our data suggest an influence of sex and age on susceptibility to AQP4-ab-positive NMO/SD. Genetic and hormonal factors might contribute to pathophysiology of NMO/SD.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/1352458516671203
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2017
    detail.hit.zdb_id: 2008225-3
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  • 8
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    Immunotherapies in neuromyelitis optica spectrum disorder: efficacy and predictors of response
    BMJ ; 2017
    In:  Journal of Neurology, Neurosurgery & Psychiatry Vol. 88, No. 8 ( 2017-08), p. 639-647
    Details
    In: Journal of Neurology, Neurosurgery & Psychiatry, BMJ, Vol. 88, No. 8 ( 2017-08), p. 639-647
    Type of Medium: Online Resource
    ISSN: 0022-3050 , 1468-330X
    URL: Article
    DOI: 10.1136/jnnp-2017-315603
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2017
    detail.hit.zdb_id: 1480429-3
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