Neuromyelitis optica spectrum disorder (NMOSD) is a group of severe inflammatory demyelinating disorders of the central nervous system that involves the optic nerve and spinal cord. Currently the ...therapeutic options for an acute attack in NMOSD are limited and rarely characterized in clinical studies. This review discussed the overall characteristics of acute attack of NMOSD, related risk factor, prognosis and management. Considering the huge unmet needs and the emergence of new therapeutic targets, we also reviewed innovative treatments that might alleviate attack damage, along with the challenges to evaluate new drug for acute attack in NMOSD.
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•Concept of NMOSD and core clinical features of diagnostic criteria changes.•Understanding of pathogenesis of NMOSD helps selection of therapeutic targets.•Acute attack/relapse of NMOSD has severe clinical consequence and risk factors.•Treatments with innovative mechanisms provide advantages over current therapies.
Background:
Fingolimod is used to reduce relapse rates in relapsing-remitting multiple sclerosis (MS). It is a sphingosine 1-phosphate (S1P) analogue having antagonistic effects on S1P receptors. Its ...immunosuppressive effect is due to reduced circulating lymphocyte numbers, and it may also be associated with impaired intrinsic cancer surveillance. Fingolimod side effects include increased rates and severity of viral infections particularly varicella zoster.
Methods:
We present five cases of chronic and treatment refractory warts associated with fingolimod therapy.
Results:
Each of the five cases presenting with chronic warts while receiving fingolimod therapy had prolonged periods of lymphopenia and improvements were seen following dose reduction or cessation of fingolimod.
Conclusion:
Cutaneous warts are associated with human papilloma virus (HPV) infection, suggesting an increased risk of other HPV-driven conditions such as cervical cancer following fingolimod administration. HPV viruses are responsible for approximately 90% of cervical cancers as well as a significant portion of anogenital cancers and have a high prevalence in sexually active adults. Given the reduced immune response to viral infections and potential impaired cancer surveillance in those receiving fingolimod, HPV vaccination and frequent assessment for the development of HPV-associated malignancies are recommended.
Altered composition of gut bacteria and changes to the production of their bioactive metabolites, the short-chain fatty acids (SCFAs), have been implicated in the development of multiple sclerosis ...(MS). However, the immunomodulatory actions of SCFAs and intermediaries in their ability to influence MS pathogenesis are uncertain. In this study, levels of serum SCFAs were correlated with immune cell abundance and phenotype as well as with other relevant serum factors in blood samples taken at first presentation of Clinically Isolated Syndrome (CIS; an early form of MS) or MS and compared to healthy controls. There was a small but significant reduction in propionate levels in the serum of patients with CIS or MS compared with healthy controls. The frequencies of circulating T follicular regulatory cells and T follicular helper cells were significantly positively correlated with serum levels of propionate. Levels of butyrate associated positively with frequencies of IL-10-producing B-cells and negatively with frequencies of class-switched memory B-cells. TNF production by polyclonally-activated B-cells correlated negatively with acetate levels. Levels of serum SCFAs associated with changes in circulating immune cells and biomarkers implicated in the development of MS.
We investigated the serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) levels in a cohort of Chinese patients with neuromyelitis optica spectrum disorders (NMOSD) and ...multiple sclerosis (MS) in relation to clinical disease course and treatment. sNfL and sGFAP levels were determined by ultrasensitive single molecule array (Simoa) assay in patients with NMOSD (n = 102) and MS (n = 98) and healthy controls (HCs; n = 84). Notably, 13 patients with NMOSD and 27 patients with MS were enrolled in the 1‐year follow‐up cohort. Levels were compared with data such as clinical course, disease duration, Expanded Disability Status Scale (EDSS) score, and lesions on MRI. Higher levels of sNfL and sGFAP were found in subjects with NMOSD and MS than in HCs (sNfL, median 12.11, 17.5 vs. 8.88 pg/ml, p < .05; sGFAP, median 130.2, 160.4 vs. 80.01 pg/ml, p < .05). Moreover, sNfL levels were higher in the relapse phase of MS than in the relapse phase of NMOSD (30.02 vs. 14.57 pg/ml, p < .05); sGFAP levels were higher in the remission phase of MS than in the remission phase of NMOSD (159.8 vs. 124.5 pg/ml, p < .01). A higher sGFAP/sNfL quotient at relapse differentiated NMOSD from MS. Multivariate analyses indicated that sGFAP levels were associated with the EDSS score in NMOSD (p < .05). At the 1‐year follow‐up, sNfL and sGFAP levels were both decreased in NMOSD patients in remission, while only sNfL levels were decreased in MS patients in remission. sGFAP and sNfL are potential blood biomarkers for diagnosing and monitoring NMOSD and MS.
Graphical representation can be used to illustrate the rationale, main results, and implications of the study. This study found higher serum levels of neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) in subjects with neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) than in controls, all were measured by single molecule array assay (Simoa). This points to the usefulness of these measures as potential blood biomarkers for these neurological disorders. Our study makes a significant contribution to the literature because present techniques of measuring sNfL and sGFAP rely on lumbar puncture, which is extremely invasive. This is a meaningful study of the application of novel neurochemical method to neuroimmune diseases and could lead to less invasive investigations, reducing the burden on patients with these diseases.
lSex, age, ethnicity and pregnancy may be intrinsic risk factors for relapse.lRecent attack, MRI finding, AQP4-IgG positivity and GFAP level may predict relapse.lOld age, severe and frequent attack ...and myelitis may suggest worse prognosis.lMonoclonal antibody therapies may be safe and more effective for relapse prevention.lRelapse prediction may assist in choosing treatment in high-relapse risk patients.
Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune inflammatory disorder of the central nervous system (CNS) that is mainly associated with serum autoantibodies against aquaporin-4 (AQP4) in astrocytes. The relapsing clinical course of NMOSD, which can be blinding and disabling due to severe visual impairment, spinal cord lesions and a group of brain syndromes, suggests the importance of accurately evaluating the likelihood and severity of relapse at an early stage of the disease. To date, many risk factors have been revealed in association with relapse, and only some of them are supported by substantial evidence. Furthermore, while the clinical use of conventional immunosuppressants is mostly empirical, an increasing number of emerging therapies for monoclonal antibodies have been confirmed by several randomized placebo-controlled trials to be effective and safe for relapse prevention. In this review, we summarize the reported risk factors that may influence the frequency, symptoms, severity and prognosis of relapse in NMOSD, as well as the efficacy and safety of emerging therapies for relapse prevention. All of these results enable us to better recognize patients who are at higher risk of relapse and suggest more effective monoclonal antibody therapies for use in these patients.
Myelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD) causes major disability as a consequence of recurrent demyelinating events and neuronal loss. Biomarkers identifying different ...phenotypes of recurrence or tissue damage might be useful to guide individualized therapy. Herein, we evaluated serum neurofilament light chain (sNfL) as a potential biomarker in both adult and pediatric MOGAD patients. Forty‐nine patients with MOGAD (37 adults, 12 children) and 71 healthy controls (HCs) (56 adults, 15 children) were enrolled prospectively from September 2019 to April 2021 at the Third Affiliated Hospital of Sun Yat‐sen University and the Children's Hospital, Zhejiang University School of Medicine. sNfL levels were determined using ultrasensitive single‐molecule array assay and correlated with clinical parameters. The sNfL levels in MOGAD adults in a relapsed state (median: 31.0 pg/ml) were higher than those in a remission state (8.1 pg/ml, p = 0.001) and in HC adults (10.3 pg/ml, p = 0.004). Similar results were observed in children (relapse: 46.8 pg/ml vs. remission: 13.1 pg/ml, p = 0.001; and vs. HCs: 8.2 pg/ml, p = 0.007) sNfL levels were correlated with recent relapses within 60 days (multivariate: β = 2.02, p = 0.003), seizures (multivariate: β = 2.50, p = 0.021) and brain lesions on magnetic resonance imaging (MRI) of a recent relapse (multivariate: β = 1.72, p = 0.012). Our study showed that sNfL levels are beneficial for identifying recent relapses and seizures and suggest that adult and pediatric MOGAD patients had similar sNfL levels.
This study determined the level of serum neurofilament light chain (sNfL) by ultrasensitive single‐molecule array assay. The authors found that the sNfL was significantly higher in relapse than in remission in both adult and pediatric patients with myelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD). sNfL levels were significantly increased in the brain phenotype in MOGAD patients compared with healthy controls and were beneficial for identifying recent relapses and seizures. These findings are of great importance because sNfL is a promising biomarker for identifying phenotypes of recurrence in MOGAD, which might be useful to guide individualized therapy and reduce burdens on patients.
The Australian multiple sclerosis (MS) community experienced two recent major crises, widespread bushfires and the COVID 19 pandemic. We aimed to understand the needs of persons with MS during times ...of crisis.
A consumer-directed mixed-method study. We included an online survey, semi-structured interviews, and a workshop with persons with MS, carers, healthcare professionals, and disability advocates. Data were collected via: (1) 176 people completing online surveys to identify crisis concerns and communications, (2) 29 people completing online interviews on bushfire and pandemic impact, and (3) 13 people participating in a crises-priorities workshop. Descriptive data were calculated for survey response, and a general inductive analytical approach was taken with interview and workshop responses.
The most significant concerns were bushfire smoke exposure and disease-modifying-medication and susceptibility to COVID-19 (66% and 63% mean concern score, respectively). Interviews indicated crises experiences from the bushfires, and the pandemic overlapped respective of changes in mood and symptom stability. For bushfires, a need for future preparations, and for the pandemic, the benefits of social restrictions, disclosing personal health information and increased care burden were important.
Multiple crises challenged the MS community but offered lessons for healthcare in future crises. Continued progress in centralised crisis information, with considered use of telehealth and rural healthcare support, is needed.
Implications for rehabilitation
The MS community showed high concerns for the effect of toxic smoke from the 2019/2020 Australian bushfires and, separately, for the disease-modifying-medication and susceptibility to COVID-19.
The MS community placed priority on a crisis management plan for individuals.
Reduced social activity due to restrictions was beneficial for MS symptom self-awareness and may help overall fatigue management.
Healthcare system preparation must prepare to alleviate increased carer workload at times of crisis.
Background and purpose
Preventing relapse by immunosuppressants (ISs) is critical for the prognosis of neuromyelitis optica spectrum disorder (NMOSD); however, the optimal duration of IS treatment is ...still under discussion. The objective was to explore the optimal duration of IS treatment and the risk of IS discontinuation for NMOSD.
Method
This cohort study was conducted at a major neurological center that housed the largest NMOSD database in South China. Eligible participants were patients with NMOSD undergoing IS treatment. The main outcome measures were changes in relapse risk based on IS treatment duration, clinical outcomes and predictors of relapse following IS discontinuation.
Results
In total, 343 patients were included in this study. The duration of IS treatment was strongly associated with a decrease in relapse risk (hazard ratio HR 0.53, p < 0.001). Continuous IS treatment resulted in decreased relapse HRs within 5 years of receiving IS medication, with a mild rebound starting at 5 years. Rituximab reduced the risk of NMOSD relapse to approximately zero within 3 years. The rate of relapse after IS withdrawal was high (77.5%). As opposed to other ISs, a delayed relapse following rituximab withdrawal was observed in this study. Longitudinal extensive transverse myelitis (HR = 2.023, p = 0.006) was associated with a higher risk of relapse after IS discontinuation.
Conclusions
Long‐term IS medication for NMOSD is generally suitable. Patients with longitudinal extensive transverse myelitis had a higher risk of relapse after IS discontinuation. Future studies should explore individualized strategies of rituximab maintenance treatment.
Continuous azathioprine/mycophenolate mofetil treatment showed a decreased trend in hazard ratio relapse within 5 years of administering medication and a mild rebound starting at the 5‐year time point, similar to that of the overall population, whilst rituximab could reduce the risk of neuromyelitis optica spectrum disorder relapse to approximately zero within 3 years.
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