Effect of late-onset on multiple sclerosis phenotype and outcome: evidence from a multi-national registry.

Although up to 20% of patients with multiple sclerosis (MS) experience onset before 18 years of age, it has been suggested that people with pediatric-onset MS (POMS) are protected against disability because of greater capacity for repair. To assess the incidence of and factors associated with progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW) in POMS compared with typical adult-onset MS (AOMS) and late-onset MS (LOMS). This cohort study on prospectively acquired data from the Italian MS Register was performed from June 1, 2000, to September 30, 2021. At the time of data extraction, longitudinal data from 73 564 patients from 120 MS centers were available in the register. The main outcomes included age-related cumulative incidence and adjusted hazard ratios (HRs) for PIRA and RAW and associated factors. Clinical and magnetic resonance imaging features, time receiving disease-modifying therapy (DMT), and time to first DMT. After applying the inclusion and exclusion criteria, the study assessed 16 130 patients with MS (median [IQR] age at onset, 28.7 [22.8-36.2 years]; 68.3% female). Compared with AOMS and LOMS, patients with POMS had less disability, exhibited more active disease, and were exposed to DMT for a longer period. A first 48-week-confirmed PIRA occurred in 7176 patients (44.5%): 558 patients with POMS (40.4%), 6258 patients with AOMS (44.3%), and 360 patients with LOMS (56.8%) (P < .001). Factors associated with PIRA were older age at onset (AOMS vs POMS HR, 1.42; 95% CI, 1.30-1.55; LOMS vs POMS HR, 2.98; 95% CI, 2.60-3.41; P < .001), longer disease duration (HR, 1.04; 95% CI, 1.04-1.05; P < .001), and shorter DMT exposure (HR, 0.69; 95% CI, 0.64-0.74; P < .001). The incidence of PIRA was 1.3% at 20 years of age, but it rapidly increased approximately 7 times between 21 and 30 years of age (9.0%) and nearly doubled for each age decade from 40 to 70 years (21.6% at 40 years, 39.0% at 50 years, 61.0% at 60 years, and 78.7% at 70 years). The cumulative incidence of RAW events followed a similar trend from 20 to 60 years (0.5% at 20 years, 3.5% at 30 years, 7.8% at 40 years, 14.4% at 50 years, and 24.1% at 60 years); no further increase was found at 70 years (27.7%). Delayed DMT initiation was associated with higher risk of PIRA (HR, 1.16; 95% CI, 1.00-1.34; P = .04) and RAW (HR, 1.75; 95% CI, 1.28-2.39; P = .001). PIRA can occur at any age, and although pediatric onset is not fully protective against progression, this study's findings suggest that patients with pediatric onset are less likely to exhibit PIRA over a decade of follow-up. However, these data also reinforce the benefit for DMT initiation in patients with POMS, as treatment was associated with reduced occurrence of both PIRA and RAW regardless of age at onset.

Background and PurposeThe incidence of multiple sclerosis (MS) among older patients is increasing. Some of these patients develop the disease after the age of 50 years, a condition known as late-onset MS (LOMS). This study aimed to characterize MS in older patients (50–75 years-old) by comparing LOMS with adult-onset MS (AOMS).MethodsWe retrospectively analyzed data from 230 patients aged 50–75 years who attended a Portuguese tertiary referral center.ResultsThis study included 189 AOMS patients aged 58 [54–63] years (median [interquartile range]) and 41 LOMS patients aged 67 [61–70] years. Females predominated in both the LOMS (70.7%) and AOMS (75.1%) groups. Primary progressive MS was more common in LOMS than AOMS patients (19.5% vs. 8.0%, p=0.03) and these two groups had equivalent proportions of relapsing-remitting MS (53.7% vs. 59.0%, p=0.55). The Expanded Disability Status Scale (EDSS) score at the diagnosis was higher in the LOMS patients (2 [1–4], p=0.03), but the current EDSS score did not differ significantly between the LOMS and AOMS patients (3.5 [1.75–6] vs. 3 [1.5–6], p=0.86). After adjusting or matching for age and disease duration, the current EDSS scores were not significantly different in the two groups. The proportion of patients currently receiving disease-modifying therapies was higher in LOMS patients (97.6%, p=0.02). A higher proportion of patients with a later onset had infratentorial involvement at a 5-year follow-up (86.7%, p=0.01). The time to an EDSS score of 6.0 was shorter for LOMS patients.ConclusionsThe LOMS patients presented with higher EDSS scores at the diagnosis, reaching a level of disability not significantly different from AOMS patients of the same age group despite a shorter disease course.

Background: Cognitive impairment is common sequelae of multiple sclerosis (MS); however, relatively little is known about cognitive impairment in late-onset multiple sclerosis (LOMS). Objective: To investigate differences in disease characteristics and cognition in LOMS and adult-onset multiple sclerosis (AOMS) patients. Methods: Archival medical records and neuropsychological evaluations from an MS specialty center were reviewed. Differences in disease characteristics between 53 LOMS and 124 AOMS were compared using chi-square or analysis of variance (ANOVA). To investigate differences in cognitive functioning, age-adjusted standardized scores were compared via analysis of covariance (ANCOVA), using cardiac risk factors and disease duration as covariates. Results: Compared to AOMS, LOMS patients had significantly more cardiac risk factors, shorter disease duration, and shorter time to diagnosis. LOMS patients had similar Expanded Disability Status Scale scores as AOMS patients. LOMS patients demonstrated significantly more impairment on tasks of visual learning and memory, and working memory than AOMS patients. Conclusion: Despite a shorter disease duration, LOMS and AOMS patients had similar levels of physical impairment. However, even after accounting for differences in disease duration and cardiac risk, LOMS patients showed a greater burden of cognitive impairment than AOMS patients, suggesting MS diagnosed later in life may progress faster due to the interaction between MS neuropathology and aging.

Clinical onset of multiple sclerosis (MS) after the age of 50 years is uncommon and associated with a less favorable natural history. The differences in long-term outcomes in patients with late-onset MS (LOMS, onset 50 years or older) and adult-onset MS (AOMS, onset 18 years or older and younger than 50 years) during the disease-modifying therapy (DMT) era have been less studied. This study aimed to compare patient characteristics, DMT exposure, and disability progression in Swedish patients with LOMS and AOMS over 2 decades (2001-2022). The nationwide Swedish MS registry was searched for patients with an onset of MS between January 1, 2001, and December 31, 2018, with symptom onset at age 18 years or older and ≥2 recorded Expanded Disability Status Scale (EDSS) scores. Clinical and demographic parameters and exposure to DMT were compared between LOMS and AOMS. Time to disability milestones (EDSS 4 and 6) was assessed using Kaplan-Meier curves and Cox proportional hazards regression models adjusted for sex, disease course, calendar year at onset, and DMT exposure. Among 8739 patients with MS who met inclusion criteria, 1,028 (11.8%) were LOMS. Primary progressive MS was more frequently diagnosed in LOMS compared with that in AOMS (25.2% vs 4.5%; p < 0.001). Most of the patients had been prescribed DMT, but more rarely in LOMS compared with AOMS (74.7% vs 95.6%; p < 0.001). Less than half of patients with LOMS had been exposed to a high-efficacy DMT (45.8%) compared with 73.5% of AOMS (p < 0.001). The risk of reaching disability milestones was greater for LOMS compared with that for AOMS (EDSS 4; adjusted hazard ratio [aHR] 2.71; 95% CI 2.22-3.30; p < 0.001, and EDSS 6; aHR 2.67; 95% CI 2.12-3.36; p < 0.001). This study distinguishes LOMS as a particularly vulnerable group and clinically supports close vigilance of these patients. Further studies are needed to assess and clarify the benefit of DMT usage in older adults with MS.

Background and Objectives: Early-onset MS (EOMS) and late-onset MS (LOMS) differ in terms of symptom presentation, disease progression, and disability outcomes. This study aims to evaluate the clinical characteristics of patients with EOMS and LOMS in Lithuania. Materials and Methods: A retrospective analysis of patients' medical records was conducted at the Lithuanian University of Health Sciences, Kaunas Clinics Department of Neurology. This study included 97 patients with multiple sclerosis, of which 34 were diagnosed with EOMS and 63 with LOMS. Results: The female/male ratio did not differ significantly in the EOMS group (1.26:1), while in the LOMS group, the female-to-male ratio was 2:1. All EOMS patients were diagnosed with relapsing-remitting multiple sclerosis (RRMS), while in the LOMS group, RRMS was observed in 55.6%, secondary progressive multiple sclerosis (SPMS) was observed in 27%, and primary progressive multiple sclerosis (PPMS) was observed in 17.4% of patients (p < 0.001). The most common initial symptoms in the EOMS group were brainstem dysfunction (50%), and sensory (38.2%) and visual (26.5%) disorders, whereas LOMS patients predominantly experienced brainstem dysfunction (50.8%) and motor impairments (47.6%). The EOMS group experienced more clinical relapses in the first year after diagnosis, along with more frequent radiological signs of disease activity compared to LOMS (p < 0.001). Both groups demonstrated a significant increase in Expanded Disability Status Scale (EDSS) score at the last follow-up visit compared to the baseline, while the LOMS group had higher EDSS scores both at the baseline and at the last follow-up compared to the EOMS group (p < 0.001). Only LOMS patients had an increase in Multiple Sclerosis Severity Score (MSSS) at the last follow-up compared to the baseline (p = 0.028), and MSSS was higher than in EOMS patients both at the baseline (p = 0.004) and the last follow-up (p < 0.001). Conclusions: There was no significant gender difference in the EOMS group, whereas in the LOMS group, females were predominant. Both groups had RRMS as the most common disease course. At the onset of MS, brainstem dysfunction was the most common symptom in both patient groups. EOMS patients had a more active disease course, in contrast to LOMS patients, who exhibited higher levels of disability, suggesting a progressive disease.

Pediatric, Adult, and Late-Onset Multiple Sclerosis Patients: A Unified Analysis of Clinical Profiles and Treatment Responses

BackgroundThe clinical characteristics of multiple sclerosis (MS) in individuals aged 65 years and older remain scarcely studied. This retrospective study compared late-onset MS (LOMS, onset ≥ 50 years) and adult-onset MS (AOMS, onset 18–49 years) in older adults with MS (OAwMS) aged ≥ 65 years.MethodsData of subjects aged ≥ 65 years with a confirmed MS diagnosis and a recorded age at onset were collected from the Finnish MS registry at Tampere University Hospital, excluding individuals with paediatric-onset MS. Demographics, disease-modifying therapy (DMT) use, relapse history and Expanded Disability Status Scale (EDSS) scores were compared between LOMS and AOMS groups.ResultsThe cohort included 248 subjects (41 LOMS, 207 AOMS). Primary progressive MS (PPMS) was more common in LOMS when compared to AOMS (41.5% vs. 12.6% at data acquisition, p < 0.001). Among subjects with a history of relapsing-remitting MS (RRMS) (32 LOMS, 178 AOMS), DMT had been used by 25.0% and 27.5% of subjects with LOMS and AOMS, and relapses after age 65 occurred in 18.8% and 7.3% of subjects with LOMS and AOMS, respectively. Subjects with LOMS discontinued DMT at an older age when compared to those with AOMS (mean 64.0 vs. 58.8 years, p = 0.04). No age-related differences in EDSS were observed after age 65.ConclusionsPPMS was more common among subjects with LOMS. Among subjects with a current or previous diagnosis of RRMS, occasional relapses were observed after age 65 in both groups, though multiple relapses were rare. These findings support the need for individualised care of OAwMS.

Cognitive outcomes in late-onset versus adult-onset Multiple Sclerosis

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) with heterogenic character. Typical age of onset is between 20 and 35 years. Clinically definite multiple sclerosis (CDMS) can occur also in patients older than 50 years. This type of MS is called Late Onset Multiple Sclerosis (LOMS). Until now, the differences in clinical course, type of first symptoms, and prognosis of LOMS have not been well established. Also the MRI characteristics of patients with LOMS have not been determined. Neither conventional nor nonconventional MRI features are known to be typical for LOMS. To investigate the MRI characteristics of LOMS patients based on conventional and non-conventional techniques. Twenty patients with LOMS were included in the study and 17 patients with typical onset of MS (TOMS) served as a comparative group. The two groups were matched in terms of disease duration and EDSS score. Conventional (T1- and T2-weighted images) and non-conventional (magnetization transfer images, proton magnetic resonance spectroscopy) MRI techniques were performed in all participants. Parameters from both techniques were compared between LOMS and TOMS groups. Patients with late onset of MS had lower Brain Parenchyma Fraction (BPF) (p < 0.001) and Grey Matter Fraction (GMF) values (p = 0.008) than the TOMS group. There was no statistical differences in White Matter Fraction (WMF) values between the groups (p = 0.572). Patients with LOMS and TOMS statistically differed in the peak height (p = 0.018), peak location (p < 0.001), and MTR mean value (p < 0.001). Patients with LOMS manifested lower concentrations of NAA+NAAG and NAA+NAAG/Cr than patients with TOMS (p = 0.009 and p < 0.001 respectively). No statistical difference was found between the groups in terms of mean mIn (p = 0.346) and mean GPC+PCh (p = 0.563). We did not find a statistical difference in T1- and T2- lesion load (p = 0.1, p = 0.3 respectively) although T1/T2 lesion ratio was higher in the LOMS group. MRI parameters in patients with LOMS differed significantly from those obtained from the TOMS group. Our results, which indicate that in LOMS patients brain tissue damage is more advanced than in TOMS patients, may contribute to a better understanding of the heterogeneity of MS.

Multiple sclerosis by phenotype in Germany

BackgroundMultiple Sclerosis typically presents in the third and fourth decades of life and was initially thought not to develop after the age of 50. However, onset after this age is...

Background: Late-onset multiple sclerosis (LOMS) frequently features a primary progressive (PP) course, strongly predicting severe disability. In this population-based cohort, we estimated the prognostic role of age at multiple sclerosis (MS) onset, independent of PP course, on disability progression. Methods: The association of age at disease onset (adult, <50 years [AOMS], vs. late, ≥50 years [LOMS]) and time to Expanded Disability Status Scale (EDSS) score 4 and 6 was estimated by Cox regression modelling. Results: Among 3,597 patients, 245 had LOMS. Relapsing-remitting (RR) disease was less frequent with LOMS than AOMS (51.8 vs. 90.8%, p < 0.0001). PP course, LOMS and male gender predicted short time to EDSS 4 and 6. Worse outcome with LOMS (time to EDSS 4 and 6, HR 2.0 [95% CI 1.7-2.4] and 2.3 [1.9-2.9]) was independent of PP course or male gender. LOMS had greater impact on RR than PP disease (time to EDSS 4 and 6, HR 3.1 [2.3-4.0] and 4.0 [2.9-5.6]). Only LOMS predicted time from EDSS 4 to 6 (p < 0.0001). Conclusions: Late onset MS was strongly associated with poor prognosis, independent of initial disease course, in predicting the disability progression along time.

Objectives: We aimed to examine the incidence and disease course of late-onset multiple sclerosis (LOMS) compared with adult-onset MS (AOMS) in our clinic cohort, stratified based on gender and race, since both have been reported as important modifiers of disease outcomes in MS. Methods: Patients with LOMS and AOMS were compared in terms of demographic characteristics and disease course characteristics. Combined effects were investigated with a logistic regression model. Time from disease onset to sustained Expanded Disability Status Scale (EDSS) score of 6 was investigated using an extension of log-rank test appropriate for interval-censored data. Results: Some 7.96% of 4273 patients studied had an onset of MS after the age of 50 years (LOMS), and 1.33% experienced an onset after age 60. Progressive onset was more common in LOMS relative to AOMS. The proportion of women with progressive-onset disease was similar in AOMS and LOMS. Time to EDSS 6 was delayed in AOMS females compared with males; however, it was similar between males and females in the LOMS group. Conclusions: Women with LOMS have a different trajectory in terms of disease progression than women with AOMS. The effect of menopause combined with race/ethnicity on the MS disease course requires further investigation.

Prognostic impact of epilepsy in multiple sclerosis

Late onset multiple sclerosis