Purpose of Review
The purpose of this review is to discuss the interaction between aging, progressive disease course, disability worsening, and treatment strategies in multiple sclerosis (MS).
Recent ...Findings
The transition from the relapsing-remitting phase to the progressive phase in MS often happens in the fifth decade. In MS, structural central nervous system reserve decreases with aging and MS-associated mechanisms. While clinical and subclinical disease activity decreases with aging, the post-relapse recovery potential decreases with aging as well. Moreover, the efficacy of disease-modifying treatments declines with older age.
Summary
Aging emerges as the ultimate target for prevention of progressive disease course, which is the most important determinant of disability worsening in MS. While none of our current treatment strategies targets the association between aging and progressive disease in MS, future treatment targets will likely consider the neuron-astrocyte complex, microglia, and oligodendrocyte functions impacted by the aging process.
Cerebellar dysfunction is likely to cause severe and treatment-resistant disability in multiple sclerosis (MS). Certain spinocerebellar ataxia (SCA)-related alleles can increase MS susceptibility, ...and channel polymorphisms can impact disability measures. Following an index patient with the coexistence of MS and SCA Type-8 (SCA8) in the MS clinic, an institutional engine search for MS and hereditary ataxia coexistence was conducted but did not reveal any other cases. This extremely rare coexistence of MS and SCA8 in our index patient may be incidental; however, a yet-to-be-identified contribution of coexistent hereditary ataxia(s) to the susceptibility of a prominent progressive ataxia MS phenotype cannot be ruled out.
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.
Objective:
To evaluate the impact of age on recovery from multiple sclerosis relapses.
Background:
Increasing disability in multiple sclerosis is a consequence of progressive disease and incomplete ...relapse recovery.
Methods:
The first and last-ever relapse data (357 relapses in 193 patients) from the Olmsted County population-based multiple sclerosis cohort were systematically reviewed for age, fulminance, location (optic nerve, brainstem/cerebellar, spinal cord), peak deficit, and maximum recovery. Three different relapse-outcome measures were studied both as paired analyses and as an overall group effect: change from peak deficit to maximum recovery in raw functional system score related to the relapse (ΔFSS), a previously published FSS-based relapse-impact model, and change from peak deficit to maximum recovery in Extended Disability Status Scale (ΔEDSS) score.
Results:
Older age was linearly associated with worse recovery in the ΔFSS outcome (p = 0.002), ΔEDSS outcome (p < 0.001), and the FSS-based relapse-impact model (p < 0.001). A multivariate analysis of ΔFSS outcome linked poor recovery to older age (p = 0.015), relapse location (transverse myelitis or brainstem/cerebellar syndrome; p < 0.001), and relapse fulminance (p = 0.004).
Conclusion:
Multiple sclerosis-relapse recovery declines in a linear fashion with increased age, which should be considered when making treatment decisions.
Clear sex differences are observed in clinical and imaging phenotypes of multiple sclerosis (MS), which evolve significantly over the age spectrum, and more specifically, during reproductive ...milestones such as pregnancy and menopause. With neuroimaging being an outcome measure and also a key subclinical biomarker of subsequent clinical phenotype in MS, this comprehensive review aims to provide an overview of sex and hormone differences in structural and functional imaging biomarkers of MS, including lesion burden and location, atrophy, white matter integrity, functional connectivity, and iron distribution. Furthermore, how therapies aimed at altering sex hormones can impact imaging of women and men with MS over the lifespan is discussed. This review also explores the key intersection between age, sex, and race/ethnicity in MS, and how this intersection may affect imaging biomarkers of MS.
Background:
We evaluated imaging features suggestive of neurodegeneration within the brainstem and upper cervical spinal cord (UCSC) in non-progressive multiple sclerosis (MS).
Methods:
Standardized ...3-Tesla three-dimensional brain magnetic resonance imaging (MRI) studies were prospectively acquired. Rates of change in volume, surface texture, curvature were quantified at the pons and medulla-UCSC. Whole and regional brain volumes and T2-weighted lesion volumes were also quantified. Independent regression models were constructed to evaluate differences between those of Black or African ancestry (B/AA) and European ancestry (EA) with non-progressive MS.
Results:
209 people with MS (pwMS) having at least two MRI studies, 29% possessing 3–6 timepoints, resulted in 487 scans for analysis. Median follow-up time between MRI timepoints was 1.33 (25th–75th percentile: 0.51–1.98) years. Of 183 non-progressive pwMS, 88 and 95 self-reported being B/AA and EA, respectively. Non-progressive pwMS demonstrated greater rates of decline in pontine volume (p < 0.0001) in B/AA and in medulla-UCSC volume (p < 0.0001) for EA pwMS. Longitudinal surface texture and curvature changes suggesting reduced tissue integrity were observed at the ventral medulla-UCSC (p < 0.001), dorsal pons (p < 0.0001) and dorsal medulla (p < 0.0001) but not the ventral pons (p = 0.92) between groups.
Conclusions:
Selectively vulnerable regions within the brainstem-UCSC may allow for more personalized approaches to disease surveillance and management.
Background:
There is growing interest in white matter (WM) imaging with positron emission tomography (PET).
Objectives:
We studied the association of cognitive function in late multiple sclerosis ...(MS) with cortical and WM Pittsburgh compound-B PET (PiB-PET) binding.
Methods:
In the population-based Mayo Clinic Study of Aging, 24 of 4869 participants had MS (12 underwent PiB-PET). Controls were age and sex matched (5:1). We used automated or semi-automated processing for quantitative image analyses and conditional logistic regression for group differences.
Results:
MS patients had lower memory (p = 0.03) and language (p = 0.02) performance; smaller thalamic volumes (p = 0.003); and thinner temporal (p = 0.001) and frontal (p = 0.045) cortices on magnetic resonance imaging (MRI) than controls. There was no difference in global cortical PiB standardized uptake value ratios between MS and controls (p = 0.35). PiB uptake was lower in areas of WM hyperintensities compared to normal-appearing white matter (NAWM) in MS (p = 0.0002). Reduced PiB uptake in both the areas of WM hyperintensities (r = 0.65; p = 0.02) and NAWM (r = 0.69; p = 0.01) was associated with decreased visuospatial performance in MS.
Conclusion:
PiB uptake in the cortex in late MS is not different from normal age-matched controls. PiB uptake in the WM in late MS may be a marker of the large network structures’ integrity such as those involved in visuospatial performance.
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