Background:
In the general population, maternal SARS-CoV-2 infection during pregnancy is associated with worse maternal outcomes; however, only one study so far has evaluated COVID-19 clinical ...outcomes in pregnant and postpartum women with multiple sclerosis, showing no higher risk for poor COVID-19 outcomes in these patients.
Objective:
In this multicenter study, we aimed to evaluate COVID-19 clinical outcomes in pregnant patients with multiple sclerosis.
Methods:
We recruited 85 pregnant patients with multiple sclerosis who contracted COVID-19 after conception and were prospectively followed-up in Italian and Turkish Centers, in the period 2020-2022. A control group of 1354 women was extracted from the database of the Multiple Sclerosis and COVID-19 (MuSC-19). Univariate and subsequent logistic regression models were fitted to search for risk factors associated with severe COVID-19 course (at least one outcome among hospitalization, intensive care unit ICU admission and death).
Results:
In the multivariable analysis, independent predictors of severe COVID-19 were age, body mass index ⩾ 30, treatment with anti-CD20 and recent use of methylprednisolone. Vaccination before infection was a protective factor. Vaccination before infection was a protective factor. Pregnancy was not a risk nor a protective factor for severe COVID-19 course.
Conclusion:
Our data show no significant increase of severe COVID-19 outcomes in patients with multiple sclerosis who contracted the infection during pregnancy.
•We studied the influence of mode of delivery and lactation on age at MS onset (AAO).•208/2055 patients (11%) were born from C-section, 563/2055 (27%) had infant formula.•C-section was associated ...with an earlier AAO (−5.2 yrs) than vaginal delivery.•Infant formula was associated with an earlier AAO (−4.2 yrs) than breastfeeding.•These associations were more apparent in patients without a family history of MS.
Mode of delivery and lactation are among the earliest factors influencing gut microbiota composition and potentially MS risk, but their contribution to MS susceptibility has been controversial. We investigated whether these factors could influence age at MS onset (AAO) on 2055 RRMS patients (mean age 28.4 years). Patients born by means of a caesarean section (10.9%) had an earlier AAO than those born through natural delivery (−5.2 years, p < 0.001). Patients fed with infant formula had an earlier AAO compared to patients breastfed, particularly considering those breastfed for at least 6 months (−4.2 years, p < 0.001). The association of vaginal delivery and natural breastfeeding with a later AAO of MS was particularly apparent in patients without a family history of MS, while disappeared in patients with familiarity for MS. The results suggest these modifiable environmental factors which act at the population level may have an influence on the onset of the disease.
Neuromyelitis optica is a rare neurological autoimmune disorder characterized by a poor prognosis. Immunosuppression can halt disease progression, but some patients are refractory to multiple ...treatments, experiencing frequent relapses with accumulating disability. Here we report on durable clinical remissions after allogeneic hematopoietic stem cell transplantation in 2 patients suffering from severe forms of the disease. Immunological data evidenced disappearance of the pathogenic antibodies and regeneration of a naive immune system of donor origin. These findings correlated with evident clinical and radiological improvement in both patients, warranting extended clinical trials to investigate this promising therapeutic option. ANN NEUROL 2014;75:447–453
We describe a patient, previously known for NMOSD, who presented a rapidly progressive worsening of muscle strength, respiratory, and bulbar functions. ALS associated with cognitive impairment was ...diagnosed, while genetic analysis revealed a hexanucleotide repeat expansion in the C9orf72 gene. To the best of our knowledge, this is the first reported C9orf72-ALS patient with concurrent NMOSD. In consideration of the low prevalence of these two diseases, a by-chance co-occurrence is unlikely. Although the discovery of a disease-specific serum AQP4-IgG antibody has led to a broadening of the NMOSD, a progressive neurological deterioration, as shown by our patient, should be considered as a "red flag", leading to alternative diagnostic hypotheses. Our report supports the hypothesis that in C9orf72-ALS neuroinflammation may contribute to disease penetrance or to determine an aggressive clinical phenotype. Further investigations are needed in order to establish possible shared neuroinflammatory patterns between ALS, NMOSD, and other neuroinflammatory disorders.
•Mobile technologies offer opportunities for real-time assessment of symptoms of MS.•Acceptability of these tools for patients needs careful consideration.•We report on the views of people with MS on ...potential barriers and facilitators.•There is a need to consider fluctuating physical status in the design of resources.•Perceived costs need addressing in the context of providing choice and control.
Smartphone apps and wearable devices could augment clinical practice by detecting changes in health status for multiple sclerosis (MS). This study sought to investigate potential barriers and facilitators for uptake and sustained use in (i) people with both relapsing remitting MS (RRMS) and progressive MS (PMS) and (ii) across different countries.
Twenty four participants with MS took part in four focus groups held in three countries (2 in the UK, 1 in Spain, and 1 in Italy) to investigate potential barriers and facilitators for mHealth technology. A systematic thematic analysis was used to extract themes and sub-themes.
Facilitators and barriers were organised into functional technology-related factors and non-functional health-related and user-related factors. Twelve themes captured all requirements across the three countries for both RRMS and PMS. Key requirements included accommodation for varying physical abilities, providing information and memory aids. Potential negative effects on mood and providing choice and control as part of overcoming practical challenges were identified.
We took a cross-national perspective and found many similarities between three European countries across people with RRMS and PMS. Future provision should accommodate the key requirements identified to engage people with MS in scalable mHealth interventions.
To determine optic nerve and retinal damage in aquaporin-4 antibody (AQP4-IgG)-seropositive neuromyelitis optica spectrum disorders (NMOSD) in a large international cohort after previous studies have ...been limited by small and heterogeneous cohorts.
The cross-sectional Collaborative Retrospective Study on retinal optical coherence tomography (OCT) in neuromyelitis optica collected retrospective data from 22 centers. Of 653 screened participants, we included 283 AQP4-IgG-seropositive patients with NMOSD and 72 healthy controls (HCs). Participants underwent OCT with central reading including quality control and intraretinal segmentation. The primary outcome was thickness of combined ganglion cell and inner plexiform (GCIP) layer; secondary outcomes were thickness of peripapillary retinal nerve fiber layer (pRNFL) and visual acuity (VA).
Eyes with ON (NMOSD-ON, N = 260) or without ON (NMOSD-NON, N = 241) were assessed compared with HCs (N = 136). In NMOSD-ON, GCIP layer (57.4 ± 12.2 μm) was reduced compared with HC (GCIP layer: 81.4 ± 5.7 μm,
< 0.001). GCIP layer loss (-22.7 μm) after the first ON was higher than after the next (-3.5 μm) and subsequent episodes. pRNFL observations were similar. NMOSD-NON exhibited reduced GCIP layer but not pRNFL compared with HC. VA was greatly reduced in NMOSD-ON compared with HC eyes, but did not differ between NMOSD-NON and HC.
Our results emphasize that attack prevention is key to avoid severe neuroaxonal damage and vision loss caused by ON in NMOSD. Therapies ameliorating attack-related damage, especially during a first attack, are an unmet clinical need. Mild signs of neuroaxonal changes without apparent vision loss in ON-unaffected eyes might be solely due to contralateral ON attacks and do not suggest clinically relevant progression but need further investigation.
Background:
Multiple sclerosis (MS) is a disease in which biomarker identification is fundamental to predict response to treatments and to deliver the optimal drug to patients. We previously found an ...association between rs7298096, a polymorphism upstream to the NINJ2 gene, and the 4-year response to interferon-β (IFNβ) treatment in MS patients.
Objectives:
To analyse the association between rs7298096 and time to first relapse (TTFR) during IFNβ therapy in MS patients and to better investigate its functional role.
Methods:
Survival analysis was applied in three MS cohorts from different countries (n = 1004). We also studied the role of the polymorphism on gene expression using GTEx portal and a luciferase assay. We interrogated GEO datasets to explore the relationship between NINJ2 expression, IFNβ and TTFR.
Results:
Rs7298096AA patients show a shorter TTFR than rs7298096G-carriers (Pmeta-analysis = 3 × 10−4, hazard ratio = 1.41). Moreover, rs7298096AA is associated with a higher NINJ2 expression in blood (p = 7.0 × 10−6), which was confirmed in vitro (p = 0.009). Finally, NINJ2 expression is downregulated by IFNβ treatment and related to TTFR.
Conclusions:
Rs7298096 could influence MS disease activity during IFNβ treatment by modulating NINJ2 expression in blood. The gene encodes for an adhesion molecule involved in inflammation and endothelial cells activation, supporting its role in MS.
Natalizumab (NTZ) is extremely effective in reducing disease activity in multiple sclerosis (MS) patients but its long-term use is associated with the risk of progressive multifocal ...leukoencephalopathy (PML). Thus, many patients discontinue NTZ and, after drug withdrawal, most of them face disease reactivation despite immunomodulant (IMD) start. The aim of this study was to evaluate the efficacy of different therapeutic strategies in preventing post-NTZ disease recurrence in a small cohort of patients that underwent repeated NTZ courses. 15 patients underwent two distinct NTZ discontinuations and started IMD after first withdrawal and a second line therapy (mainly fingolimod, FTY) after the second one. They were followed with periodic clinical and neuroradiological evaluations. All patients showed disease reactivation after first withdrawal and 13 out of 15 relapsed after the second one. In both the occasions annualized relapse rate (ARR) significantly increased as compared to on-treatment period (from 0.03 to 1.5 and from 0.26 to 1.71) with no differences between the two NTZ-free periods. Likewise, the mean number of Gd enhancing lesions increased both times to similar values (3.1 and 2.9). Median time to disease recurrence was comparable (4.7 and 5.7 months,
p
= 0.57). This study demonstrated recurrence of disease activity after two distinct NTZ discontinuations despite the treatment with IMD or more aggressive therapy, when used according to recent safety recommendations. Therefore, we need different therapeutic strategies to cope with the risk of post-NTZ disease recurrence and a “bridging strategy” with an earlier switch to second line drugs should be taken into account.
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