Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating central nervous system disorder that is more common in women, with onset often during reproductive years. The female:male sex ratio ...of MS rose in several regions over the last century, suggesting a possible sex by environmental interaction increasing MS risk in women. Since many with MS are in their childbearing years, family planning, including contraceptive and disease-modifying therapy (DMT) counselling, are important aspects of MS care in women. While some DMTs are likely harmful to the developing fetus, others can be used shortly before or until pregnancy is confirmed. Overall, pregnancy decreases risk of MS relapses, whereas relapse risk may increase postpartum, although pregnancy does not appear to be harmful for long-term prognosis of MS. However, ovarian aging may contribute to disability progression in women with MS. Here, we review sex effects across the lifespan in women with MS, including the effect of sex on MS susceptibility, effects of pregnancy on MS disease activity, and management strategies around pregnancy, including risks associated with DMT use before and during pregnancy, and while breastfeeding. We also review reproductive aging and sexual dysfunction in women with MS.
Neuromyelitis optica spectrum disorder (NMOSD), autoimmune encephalitis (AE), myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) are antibody-mediated neurological diseases. They ...have mostly female predominance, affecting many women during childbearing age. Interactions between the underlying disease (or necessary treatment) and pregnancy can occur in every of these illnesses. Herein, we present the characteristics of NMOSD, AE, MG and LEMS in general, and review published data regarding the influence of the different diseases on fertility, pregnancy, puerperium, treatment strategy during pregnancy and post-partum period, and menopause but also male factors. We summarise key elements that should be borne in mind when confronted with such cases.
To evaluate the changes in visual acuity (VA) and central macular thickness (CMT) after intravitreal dexamethasone (IVD) implantation in intravitreal bevacizumab (IVB) treatment-resistant cases with ...pseudophakic cystoid macular edema (PCME).
This study included 10 PCME cases who underwent uneventful phacoemulsification and intraocular lens implantation with similar methods and six PCME cases referred to our hospital for treatment of low VA after cataract surgery. Due to the persistence of PCME, both topical steroid and anti-inflammatory medication were administered first, followed by IVB injection. IVD implantation was performed for all IVB treatment-resistant cases. VA and CMT values were compared before and at three months after the first IVD implantation.
The mean VA values before and at 3 months after the first IVD implantation were 0.69 ± 0.19 logarithm of the minimum angle of resolution (logMAR) (1.50 to 0.10 logMAR) and 0.26 ± 0.07 logMAR (1.00 to 0.00 logMAR), respectively (
< 0.001). The mean CMT was 476.13 ± 135.13 mm (314 to 750 mm) and 294.06 ± 15.26 mm (222 to 480 mm), respectively (
< 0.001). The mean number of implanted IVD was 1.44 ± 0.89 (1 to 4) and the mean follow-up time was 7.4 ± 4.6 months (6 to 24 months). After IVD implantation therapy, the mean VA and CMT values were 0.19 ± 0.05 logMAR (0.70 to 0.00 logMAR) and 268.38 ± 31.35 mm (217 to 351 mm), respectively.
To the best of our knowledge, this is the first report to show the efficacy of IVD implantation even after repeated IVB injections in treatment-resistant PCME. IVD implantation is both a safe and effective method for decreasing PCME after both uneventful and complicated cataract surgery.
BACKGROUND:Fingolimod withdrawal may trigger the return of pretreatment disease activity. It is difficult to identify patients at risk of disease reactivation. We compared the demographic and ...clinical features of patients experiencing severe disease reactivation (SDR) after fingolimod cessation with those of patients who did not.
METHODS:All patients who commenced fingolimod and who continued therapy for at least 6 months were included. The demographic and clinical features of the 2 groups (SDR vs. no SDR) were assessed.
RESULTS:Forty-four of 303 patients discontinued fingolimod for various reasons. Among these, 31 fulfilled our inclusion criteria and 8 (25.8%) exhibited SDR after drug cessation. The mean time for SDR was 2.6 months (range, 2 to 3 mo). The annualized relapse rate before fingolimod therapy was higher in the SDR than in the non-SDR group (1.59 vs. 0.81) (P=0.018). Although statistical significance was not attained, the mean Expanded Disability Status Scale score at the time of fingolimod cessation was higher in the non-SDR than in the SDR group (2.5 vs. 1.12) (P=0.074).
CONCLUSIONS:SDR may develop within the first 3 months after cessation of fingolimod. Patients with higher annualized relapse rates and lower Expanded Disability Status Scale scores before commencing fingolimod treatment were more likely to exhibit SDR.
Background:
Effectiveness of cladribine tablets, an oral disease-modifying treatment (DMT) for multiple sclerosis (MS), was established in clinical trials and confirmed with real-world experience.
...Objectives:
Use real-world data to compare treatment patterns and clinical outcomes in people with MS (pwMS) treated with cladribine tablets versus other oral DMTs.
Methods:
Retrospective treatment comparisons were based on data from the international MSBase registry. Eligible pwMS started treatment with cladribine, fingolimod, dimethyl fumarate, or teriflunomide tablets from 2018 to mid-2021 and were censored at treatment discontinuation/switch, death, loss to follow-up, pregnancy, or study period end. Treatment persistence was evaluated as time to discontinuation/switch; relapse outcomes included time to first relapse and annualized relapse rate (ARR).
Results:
Cohorts included 633 pwMS receiving cladribine tablets, 1195 receiving fingolimod, 912 receiving dimethyl fumarate, and 735 receiving teriflunomide. Individuals treated with fingolimod, dimethyl fumarate, or teriflunomide switched treatment significantly more quickly than matched cladribine tablet cohorts (adjusted hazard ratio (95% confidence interval): 4.00 (2.54–6.32), 7.04 (4.16–11.93), and 6.52 (3.79–11.22), respectively). Cladribine tablet cohorts had significantly longer time-to-treatment discontinuation, time to first relapse, and lower ARR, compared with other oral DMT cohorts.
Conclusion:
Cladribine tablets were associated with a significantly greater real-world treatment persistence and more favorable relapse outcomes than all oral DMT comparators.
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) with a profound neurodegenerative component early in the disease pathogenesis. Age is a factor with a ...well-described effect on the primary disease phenotype, namely, the relapsing-remitting vs. the primary progressive disease. Moreover, aging is a prominent factor contributing to the transition from relapsing-remitting MS (RRMS) to secondary progressive disease. However, sex also seems to, at least in part, dictate disease phenotype and evolution, as evidenced in humans and in animal models of the disease. Sex-specific gene expression profiles have recently elucidated an association with differential immunological signatures in the context of experimental disease. This review aims to summarize current knowledge stemming from experimental autoimmune encephalomyelitis (EAE) models regarding the effects of sex, either independently or as a factor combined with aging, on disease phenotype, with relevance to the immune system and the CNS.
Background:
Family planning and pregnancy decisions are key considerations in the management of women with multiple sclerosis (MS), who are typically diagnosed between the ages of 20–40 years. ...Despite a strong evidence base that pregnancy is not harmful for women with MS, many knowledge gaps remain. These include: best management strategies through pregnancy in the era of highly effective disease-modifying therapies (DMT); foetal risks associated with DMT exposure in utero or in relation to breastfeeding; knowledge base around the use of assisted reproductive technologies; the long-term impact of pregnancy on disease outcomes, as well as the impact of long-term DMT use on women’s health and cancer risk.
Methods:
Here, we describe the new MSBase pregnancy, neonatal outcomes and women’s health registry. We provide the rationale for, and detailed description of, the variables collected within the registry, together with data acquisition details.
Conclusion:
The present paper will act as a reference document for future studies.
Background:
Cerebellar and brainstem symptoms are common in early stages of multiple sclerosis (MS) yet their prognostic values remain unclear.
Objective:
The aim of this study was to investigate ...long-term disability outcomes in patients with early cerebellar and brainstem symptoms.
Methods:
This study used data from MSBase registry. Patients with early cerebellar/brainstem presentations were identified as those with cerebellar/brainstem relapse(s) or functional system score ⩾ 2 in the initial 2 years. Early pyramidal presentation was chosen as a comparator. Andersen-Gill models were used to compare cumulative hazards of (1) disability progression events and (2) relapses between patients with and without early cerebellar/brainstem symptoms. Mixed effect models were used to estimate the associations between early cerebellar/brainstem presentations and expanded disability status scale (EDSS) scores.
Results:
The study cohort consisted of 10,513 eligible patients, including 2723 and 3915 patients with early cerebellar and brainstem symptoms, respectively. Early cerebellar presentation was associated with greater hazard of progression events (HR = 1.37, p < 0.001) and EDSS (β = 0.16, p < 0.001). Patients with early brainstem symptoms had lower hazard of progression events (HR = 0.89, p = 0.01) and EDSS (β = −0.06, p < 0.001). Neither presentation was associated with changes in relapse risk.
Conclusion:
Early cerebellar presentation is associated with unfavourable outcomes, while early brainstem presentation is associated with favourable prognosis. These presentations may be used as MS prognostic markers and guide therapeutic approach.
Background:
The Multiple Sclerosis Severity Score (MSSS) is a widely used measure of the disability progression rate. However, the global MSSS may not be the best basis for comparison between all ...patient groups.
Objective:
We evaluated sex-specific and onset phenotype–specific MSSS matrices to determine if they were more effective than the global MSSS as a basis for comparison within these subsets.
Methods:
Using a large international dataset of multiple sclerosis (MS) patient records and the original MSSS algorithm, we constructed global, sex-specific and onset phenotype–specific MSSS matrices. We compared matrices using permutation analysis.
Results:
Our final dataset included 30,203 MS cases, with 28.9% males and 6.5% progressive-onset cases. Our global MSSS matrix did not differ from previously published data (p > 0.05). The progressive-onset-specific matrix differed significantly from the relapsing-onset-specific matrix (p < 0.001), with lower MSSS attributed to cases with the same Expanded Disability Status Score (EDSS) and disease duration. When evaluated with a simulation, using an onset-specific MSSS improved statistical power in mixed cohorts. There were no significant differences by sex.
Conclusion:
The differences in the disability accrual rate between progressive- and relapsing-onset MS have a significant effect on MSSS. An onset-specific MSSS should be used when comparing the rate of disability progression among progressive-onset cases and for mixed cohorts.
Purpose: Despite its implications for quality of life, temperament, and character in multiple sclerosis are underexplored. We aimed to explore temperament and character traits, their association with ...clinical characteristics, and explore the factors that impact depression in patients with relapsing-remitting multiple sclerosis (RRMS).Material and Methods: This cross-sectional study enrolled 67 patients (male/female=12/55) (median age=30 (18-53)) and 50 age-and gender-matched healthy controls (HCs) (male/female=16/34) (median age= 26.5 (18-60)) using a convenience sampling method. Temperament and Character Inventory, Beck Depression and Beck Anxiety Inventories, and Structured Clinical Interview for DSM-Axis I Disorders-SCID-I were applied. Results: In the patient group there were 45 MS patients with no psychiatric comorbidity (MSN) and 22 MS patients with psychiatric comorbidity (MSP). Higher self-forgetfulness was observed in the MSP group compared with MSN and HC groups. MSP and MSN demonstrated higher total harm avoidance than HCs. MSP group showed lower total self-directedness compared with HCs. While EDSS, duration of disease, or the number of relapses did not impact depression scores; higher anxiety (Β=0.416) and lower purposefulness (Β=-1.565) significantly impacted them (R2=.50, F=32.459). Conclusion: Temperament and character differences were observed in patients with and without psychiatric comorbidity. Higher anxiety levels and the difficulty to establish and attain meaningful goals may relate to higher depression levels. Future studies with larger samples examining coping, health behaviors, and resilience as potential mediators or moderators between self-forgetfulness and psychiatric disorders may aid in defining interventions for psychiatric disorders. Adequate treatment of anxiety symptoms and addressing purposefulness are potential targets for planning behavioral interventions.
Amaç: Yaşam kalitesi üzerindeki etkilerine rağmen, multipl sklerozda mizaç ve karakter yeterince araştırılmamıştır. Mizaç ve karakter boyutlarını, i, bunların klinik özelliklerle ilişkisini ve depresyon şiddetini etkileyen faktörleri tekrarlayan ve düzelen multiple skleroz (TDMS) hastalarında incelemeyi amaçladık. Gereç ve Yöntem: Bu kesitsel çalışmaya, elverişli örnekleme yöntemiyle 67 hasta (erkek/kadın=12/55) (medyan yaş=30 (18-53)) ve yaş ve cinsiyet açısından eşleştirilmiş 50 sağlıklı kontrol (SK) (erkek/kadın=16/34) (medyan yaş= 26.5 (18-60)) alındı. Mizaç ve Karakter Envanteri, Beck Depresyon ve Beck Anksiyete Envanterleri, DSM-Eksen I Bozuklukları için Yapılandırılmış Klinik Görüşme uygulandı. Bulgular: Hasta grubu içinde, psikiyatrik komorbiditesi olan 45 (MSP), psikiyatrik komorbiditesi olmayan (MSO) 22 hasta bulunuyordu. MSP grubu, MSO grubuna ve SK’lere göre daha yüksek kendilik kaybı gösterdi. MSP grubu ve MSO grubu toplam zarardan kaçınma puanları SK’lere kıyasla yüksekti. Toplam kendini yönetme puanları MSP grubunda SK’lerden düşüktü. EDSS, hastalık süresi, toplam nüks sayısı depresyon şiddetini etkilemezken; yüksek anksiyete (Β=0,416) ve düşük amaçlılık düzeyleri (Β=-1,565) depresyon düzeyini anlamlı derecede etkilemekteydi (R2=0.50, F=32.459). Sonuç: Komorbid psikiyatrik bozukluğu olan ve olmayan hastalar arasında mizaç ve karakter özellikleri açısından farklılıklar gözlendi. Artmış anksiyete düzeyleri; anlamlı hedefler belirleme ve bunlara ulaşmada güçlük, artmış depresyon düzeyleriyle ilişkili olabilir. Gelecek çalışmalar, daha geniş örneklemlerde, baş etme, sağlık davranışları ve dayanıklılığın kendilik kaybı ve psikiyatrik bozukluklar arasındaki aracı ve düzenleyici rolünü inceleyerek, psikiyatrik bozukluklara yönelik müdahalelerin tanımlanmasına yardımcı olabilir. Anksiyete belirtilerinin etkin tedavisi ve yaşam amaçlarının ele alınması, davranışsal müdahalelerin planlanması için olası hedeflerdir.
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