Multiple Sclerosis Journal最新文献

Background: The complement system has been suspected to play a role in multiple sclerosis (MS) due to presence of complement activation products in MS lesions.

Objective: We sought to understand whether variation in the complement component 4 (C4) gene is associated with MS.

Methods: Here we used next-generation sequencing and our novel bioinformatics tool, C4Investigator, to interrogate C4 copy number variation in MS.

Results: We found higher overall copy number of C4 in controls (p < 10^-16, odds ratio (OR) = 0.43, 95% confidence interval (CI): 0.37-0.49) compared to MS patients with European ancestry.

Conclusion: This finding suggests that lower C4 copies confer risk for MS, similar to associations seen in other autoimmune disorders.

The 2024 McDonald Criteria now include the optic nerve as the fifth topography for dissemination in space. Optical coherence tomography (OCT) is a valuable biomarker for the diagnosis, prognosis and monitoring of multiple sclerosis (MS). A panel of MS neurologists from 19 centres across 9 Latin American (LATAM) countries discussed OCT use, access, standardized protocols and research potential. They found inequities in OCT access between private (80%) and public healthcare (44%). Only 9 centres had standardized protocols, 50% of which followed the OSCAR-IB consensus criteria for retinal OCT quality assessment and 53% had a neuro-ophthalmologist. The panel concluded that OCT should be available in all MS centres and that standardized acquisition and reporting, as well as improved knowledge of OCT use, in clinical practice are necessary. OCT has significant research potential in LATAM that requires further development and implementation.

Background: Pediatric-onset multiple sclerosis (POMS) constitutes ~5% of multiple sclerosis (MS) cases and presents distinct clinical and diagnostic challenges. Puberty, characterized by significant hormonal changes, may influence disease presentation, relapse rates, and long-term outcomes.

Objectives: To investigate the impact of pubertal stages on clinical characteristics, relapse activity and disability progression in POMS using data from the Danish MS Registry (DMSR).

Methods: A nationwide cohort of 185 POMS patients were included and categorized by pre- (<11 years), peri- (11-14 years), and post-pubertal (>14 years) onset. Demographics, presenting symptoms, magnetic resonance imaging (MRI) findings, relapse rates, and Expanded Disability Status Scale (EDSS) scores were compared. Patients transitioning across the three pubertal stages (n = 54) were analyzed longitudinally for relapse rate.

Results: Pre-pubertal onset was associated with severe symptoms (cerebellar involvement, p = 0.042), greater lesion burden, higher 10-year disability (EDSS median = 3.75, p = 0.039), and lower relapse rates (annualized relapse rate (ARR) = 0.200). Male sex reduced relapse rates (p = 0.013). Female-to-male ratio increased from 1:1 pre-puberty to ~2:1 after puberty. Patients with pre-pubertal onset transitioning to peri- or post-puberty showed increasing relapse rates, peaking during peri-puberty (ARR = 0.302).

Conclusions: Puberty significantly modulates disease course in POMS, emphasizing the need for early, sex-specific interventions, proactive monitoring, and further exploration of hormonal influences on disease progression and treatment response.

Background: While there is increasing understanding of the effect of pregnancy on the clinical course of multiple sclerosis (MS), there are limited studies focused on younger populations.

Cases: We report neurologic and obstetric outcomes for 14 pregnancies from 11 adolescent and young adult female patients with pediatric-onset MS who delivered live births prior to age 26, and describe their relevant social determinants of health.

Conclusion: Neurologic and obstetric outcomes in this cohort were generally good. Many of the pregnancies in our cohort appeared unplanned, underscoring the importance of discussing family planning with all MS patients of childbearing potential.

Background: Research on the optimal duration of immunosuppressive therapy (IST) and the outcome upon its discontinuation in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) remains limited.

Objective: To evaluate the outcomes following IST discontinuation in MOGAD.

Methods: This multicenter retrospective study collected data from 333 MOGAD patients in Korea. Among 273 patients who received IST, 41 who discontinued IST were analyzed.

Results: The median age at disease onset was 38.3 years (interquartile range (IQR), 27.6-53.1). Before IST withdrawal, 21 (51%) patients exhibited relapsing courses. Over a median follow-up of 23.5 months (IQR, 12.1-39.5) after discontinuation, 10 patients (24.4%) relapsed after a median of 8.2 months (IQR, 6.3-11.5). All relapses occurred in patients with a prior relapsing course (10/21, 47.6%); none with prior monophasic courses relapsed. Among 21 prior relapsing patients, relapse after discontinuation group had a shorter IST duration than non-relapse group (median, 9.4 vs 50.9 months, p = 0.036). None of the 41 patients had severe disability (Expanded Disability Status Scale (EDSS) score ⩾ 4.0 or Visual Functional System score ⩾ 5) at the last visit.

Conclusion: IST discontinuation did not necessarily lead to relapse and could be considered with an individualized approach based on factors such as disease course and IST duration.

Introduction: The 2024 McDonald criteria for diagnosing multiple sclerosis (MS) include optic nerve involvement as a fifth region for establishing dissemination in space. Optic neuritis (ON) can be detected through optical coherence tomography (OCT) using an inter-eye absolute or percentage difference (IEAD, IEPD) in ganglion cell-inner plexiform layer (GCIPL) thickness.

Objective: To compare the diagnostic accuracy of GCIPL IEAD/IEPD with GCL and IPL IEAD/IEPD alone for identifying a history of ON.

Methods: This cross-sectional retrospective study included people with MS (pwMS) who underwent an OCT scan. Diagnostic accuracy was assessed using ROC analysis.

Results: A total of 241 pwMS (mean age 34.7 years [SD 9.7], 70.1% female) were included. Sixty-eight (28.2%) patients had a documented history of unilateral ON. GCL IEAD (AUC 0.79, cut-off ⩾ 0.06 mm³ or ⩾2µm, 58.9% sensitivity, 85.1% specificity) and IEPD (AUC 0.80, cut-off ⩾ 3%, 48.7% sensitivity, 89.8% specificity) demonstrated excellent diagnostic accuracy for unilateral ON, showing non-inferiority to the established GCIPL IEAD/IEPD.

Conclusion: GCL IEAD and IEPD provide strong diagnostic accuracy for identifying unilateral ON and can be effectively used as an alternative to GCIPL IEAD/IEPD to facilitate implementation in clinical routine.

Background: Investigations of a prodrome in multiple sclerosis (MS) usually have included adults.

Objective: To compare rates and reasons for health care use in youth with and without MS, considering time relative to the MS index date and to birth.

Methods: This retrospective cohort study used population-based administrative data (1991-2020) from Ontario, Canada. We matched youth (<18 years) with MS up to 5:1 to youth without MS by sex, birth year, region, and duration of observation (full cohorts). Subcohorts had data from birth to MS index date (first demyelinating disease claim). We compared health services use, adjusting for age, sex, area-level income, region, and year.

Results: We included 451 individuals with pediatric-onset MS and 1422 without MS. As of 6 years pre-index, the full MS cohort had higher physician services use (year 6: rate ratio (RR) = 1.45; 95% confidence interval (95% CI) = 1.25-1.67) and hospitalizations (RR = 2.79; 95% CI = 1.31-5.94). Findings were similar in subcohorts. The MS subcohort had elevated physician visit rates in early life that rose as the MS index date approached.

Discussion: Youth with pediatric-onset MS exhibit increased health care use from birth. Early life may be a risk period for MS. A prodromal phase may emerge 6 years before the onset of typical MS symptoms.

Background: Previous work has demonstrated that higher levels of physical activity (PA) are associated with better retinal fiber integrity in children with multiple sclerosis (MS).

Objective: To determine whether high PA levels are associated with retinal fiber integrity through time in children with demyelinating disease.

Methods: Children with MS or monophasic acquired demyelinating syndromes (mono-ADS) were included. PA level was assessed by questionnaire, and a spectral-domain optical coherence tomography (OCT) scanner determined retinal nerve and ganglion cell inner plexiform fiber layer thickness (RNFL and GCIPL, respectively). Linear mixed models were used to analyze longitudinal associations.

Results: Children with MS (n = 28, 20F, mean age 14.6 (standard deviation (SD) ±2.4)) and mono-ADS (n = 24, 11F, mean age 9.5 (SD ±4.5)) took part. In children with MS, RNFL and GCIPL thickness was shown to decline by 1.0 mm (p < 0.05) over time. More active children with MS had thicker GCIPL through time compared to those who were inactive (2.5 mm, p < 0.01). Furthermore, taking part in any strenuous PA was associated with greater RNFL and GCIPL thickness (1.5-2.1 mm, p < 0.05). These differences were not found in children with mono-ADS.

Conclusion: Moderate to vigorous PA is associated with better retinal integrity over time in pediatric MS. Future interventions should evaluate whether changes to PA level coincide with changes to retinal integrity in children with MS.