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Progress in Neurobiology Mar 2024Demyelination stands out as a prominent feature in individuals with specific types of epilepsy. Concurrently, individuals with demyelinating diseases, such as multiple... (Review)
Review
Demyelination stands out as a prominent feature in individuals with specific types of epilepsy. Concurrently, individuals with demyelinating diseases, such as multiple sclerosis (MS) are at a greater risk of developing epilepsy compared to non-MS individuals. These bidirectional connections raise the question of whether both pathological conditions share common pathogenic mechanisms. This review focuses on the reciprocal relationship between epilepsy and demyelination diseases. We commence with an overview of the neurological basis of epilepsy and demyelination diseases, followed by an exploration of how our comprehension of these two disorders has evolved in tandem. Additionally, we discuss the potential pathogenic mechanisms contributing to the interactive relationship between these two diseases. A more nuanced understanding of the interplay between epilepsy and demyelination diseases has the potential to unveiling the molecular intricacies of their pathological relationships, paving the way for innovative directions in future clinical management and treatment strategies for these diseases.
Topics: Humans; Demyelinating Diseases; Multiple Sclerosis; Epilepsy
PubMed: 38378072
DOI: 10.1016/j.pneurobio.2024.102588 -
Journal of Neurology, Neurosurgery, and... Dec 2023Whether progression independent of relapse activity (PIRA) heralds earlier onset of secondary progressive multiple sclerosis (SPMS) and more rapid accumulation of... (Observational Study)
Observational Study
BACKGROUND
Whether progression independent of relapse activity (PIRA) heralds earlier onset of secondary progressive multiple sclerosis (SPMS) and more rapid accumulation of disability during SPMS remains to be determined. We investigated the association between early PIRA, relapse-associated worsening (RAW) of disability and time to SPMS, subsequent disability progression and their response to therapy.
METHODS
This observational cohort study included patients with relapsing-remitting multiple sclerosis (RRMS) from the MSBase international registry across 146 centres and 39 countries. Associations between the number of PIRA and RAW during early multiple sclerosis (MS) (the initial 5 years of MS onset) were analysed with respect to: time to SPMS using Cox proportional hazards models adjusted for disease characteristics; and disability progression during SPMS, calculated as the change of Multiple Sclerosis Severity Scores over time, using multivariable linear regression.
RESULTS
10 692 patients met the inclusion criteria: 3125 (29%) were men and the mean MS onset age was 32.2 years. A higher number of early PIRA (HR=1.50, 95% CI 1.28 to 1.76, p<0.001) and RAW (HR=2.53, 95% CI 2.25 to 2.85, p<0.001) signalled a higher risk of SPMS. A higher proportion of early disease-modifying therapy exposure (per 10%) reduced the effect of early RAW (HR=0.94, 95% CI 0.89 to 1.00, p=0.041) but not PIRA (HR=0.97, 95% CI 0.91 to 1.05, p=0.49) on SPMS risk. No association between early PIRA/RAW and disability progression during SPMS was found.
CONCLUSIONS
Early disability increase during RRMS is associated with a greater risk of SPMS but not the rate of disability progression during SPMS. The deterioration associated with early relapses represents a potentially treatable risk factor of SPMS.
TRIAL REGISTRATION NUMBER
Australian New Zealand Clinical Trials Registry (ACTRN12605000455662).
Topics: Male; Humans; Adult; Female; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis; Disease Progression; Australia; Multiple Sclerosis, Relapsing-Remitting; Recurrence
PubMed: 37414538
DOI: 10.1136/jnnp-2023-331748 -
Journal of Neurology, Neurosurgery, and... Sep 2023We aim to evaluate whether fertility, pregnancy, delivery and breastfeeding have been actually improving in women with multiple sclerosis (MS), compared with general...
BACKGROUND
We aim to evaluate whether fertility, pregnancy, delivery and breastfeeding have been actually improving in women with multiple sclerosis (MS), compared with general population, and in relation to treatment features.
METHODS
We included 2018-2020 population-level healthcare data on women with MS living in the Campania region (Italy). Fertility, pregnancy and delivery outcomes were obtained from Certificate of Delivery Assistance; breastfeeding was collected up to 6 months after delivery by trained personnel.
RESULTS
Out of 2748 women with MS in childbearing age, 151 women delivered 156 babies. Fertility rate was 0.58 live births per woman with MS, compared with 1.29 in Campania region and 1.25 in Italy. Disease-modifying treatment (DMT) continuation during pregnancy was associated with lower birth weight (coeff -107.09; 95% CI -207.91 to -6.26; p=0.03). Exposure to DMTs with unknown/negative effects on pregnancy was associated with birth defects (OR 8.88; 95% CI 1.35 to 58.41; p=0.02). Birth defects occurred in pregnancies exposed to dimethyl fumarate (2/21 exposed pregnancies), fingolimod (1/11 exposed pregnancies) and natalizumab (2/30 exposed pregnancies). After delivery, 18.8% of women with MS were escalated of DMT efficacy, while 50.7% started on same/similar-efficacy DMTs, and 30.5% did not receive DMT. The probability of breastfeeding was higher in women who were treated with breastfeeding-safe DMTs (OR 5.57; 95% CI 1.09 to 28.55; p=0.03).
CONCLUSIONS
Fertility rate in women with MS remains below the general population. Family planning and subsequent DMT decisions should aim to achieve successful pregnancy, delivery and breastfeeding outcomes, while controlling disease activity.
Topics: Pregnancy; Humans; Female; Multiple Sclerosis; Fingolimod Hydrochloride; Natalizumab; Fertility; Dimethyl Fumarate
PubMed: 37068930
DOI: 10.1136/jnnp-2022-330883 -
Neurology Sep 2023
Topics: Humans; Multiple Sclerosis; Tomography, Optical Coherence; Multiple Sclerosis, Chronic Progressive; Retinal Degeneration; Atrophy; Retina
PubMed: 37460230
DOI: 10.1212/WNL.0000000000207607 -
Multiple Sclerosis and Related Disorders Nov 2023In this cross sectional study, we used MRF to investigate tissue properties of normal-appearing white matter, gray matter, and lesions in relapsing remitting MS...
BACKGROUND
In this cross sectional study, we used MRF to investigate tissue properties of normal-appearing white matter, gray matter, and lesions in relapsing remitting MS (n = 21), secondary progressive MS (n = 16) and healthy controls (n = 9). A FISP-based MRF sequence was used for acquisition, imaging time 5 min 15 s. MRF T1 and T2 relaxation times were measured from lesional tissue, normal-appearing frontal white matter, corpus callous, thalamus, and caudate. Differences between healthy controls and MS were examined using ANCOVA adjusted for age and sex. Spearman rank correlations were assessed between T1 and T2 relaxation times and clinical measures.
OBJECTIVES
To examine brain T1 and T2 values using magnetic resonance fingerprinting (MRF) in healthy controls and MS.
METHODS
The subjects included 21 relapsing-remitting (RR) MS, 16 secondary progressive (SP) MS, and 9 age- and sex-matched HC without manifest neurological disease participating in a longitudinal MRI study. A 3T/ FISP-based MRF sequence was acquired. Regions of interest were drawn for lesions and normal appearing white matter. ANCOVA adjusted for age and sex were used to compare the groups with significance set at 0.05.
RESULTS
A step-wise increase in T1 and T2 relaxation times was found between healthy controls, relapsing remitting MS, and secondary progressive MS. Significant differences were found in T1 and T2 between MS and healthy controls in the frontal normal-appearing white matter, corpus callosum, and thalamus (p < 0.04 for all). Significant differences in T1 and T2 between RR and SPMS were found in the frontal normal-appearing white matter and T2 lesions (p < 0.02 for all). T1 relaxation from the frontal normal-appearing white matter correlated with the Expanded Disability Status Scale [ρ = 0.62, p < 0.001], timed 25 foot walk (ρ = 0.45, p = 0.01), 9 hole peg test (ρ = 0.62, p < 0.001), and paced auditory serial addition test (ρ = -0.4, p = 0.01).
CONCLUSION
These results suggest that MRF may be a clinically feasible quantitative approach for characterizing tissue damage in MS.
Topics: Humans; Multiple Sclerosis; Cross-Sectional Studies; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Brain; Multiple Sclerosis, Relapsing-Remitting
PubMed: 37783196
DOI: 10.1016/j.msard.2023.105024 -
Neurologia I Neurochirurgia Polska 2024Assessment of the clinical course, neuroimaging and histopathological changes suggests that multiple sclerosis (MS) should not be defined merely as a focal inflammatory... (Review)
Review
INTRODUCTION
Assessment of the clinical course, neuroimaging and histopathological changes suggests that multiple sclerosis (MS) should not be defined merely as a focal inflammatory disease of the central nervous system (CNS) because the essence of the disease is due to a diffuse, 'smouldering', pathophysiological process.
STATE OF THE ART
Progression independent of relapse activity (PIRA) is the clinical indicator of smouldering MS. Multiple pathomechanical factors determining smouldering MS have been identified, i.e. continuous activation of microglia, which is the source of smouldering inflammation and the failure of remyelination in MS.
CLINICAL IMPLICATIONS
Our paper presents new neuroimaging markers, including paramagnetic rim lesions (PRLs) and slowly expanding lesions (SELs), potential methods for clinical evaluation and promising therapeutic options, i.e. Bruton's tyrosine kinase inhibitors that prevent PIRA in smouldering MS. With the duration of MS, the efficacy of the current immunomodulatory treatment is reduced, and its effect is insufficient to control smouldering MS.
FUTURE DIRECTIONS
Innovative insights into the pathophysiology and clinical course warrant the need for a holistic approach to MS. The efforts of clinicians should be aimed at indicating subtle neurological deficits in physical performance and cognitive functioning to characterise the disease progression in its early stages. Undoubtedly, a new era for MS is coming in which new resonance markers will be used together with clinical methods to assess smouldering MS, and the treatment will include combination therapy with consideration of drugs that reduce relapse rates and therapy aimed at inhibiting disease progression.
Topics: Humans; Multiple Sclerosis; Disease Progression; Neuroimaging; Magnetic Resonance Imaging
PubMed: 38842128
DOI: 10.5603/pjnns.98592 -
Neurology Sep 2023
Topics: Humans; Multiple Sclerosis; Brain; Multiple Sclerosis, Relapsing-Remitting; Head; Magnetic Resonance Imaging
PubMed: 37468283
DOI: 10.1212/WNL.0000000000207754 -
Neurologic Clinics Feb 2024Multiple sclerosis has historically been characterized as a disease that affects young women of European ancestry, but recent studies indicate that the incidence and... (Review)
Review
Multiple sclerosis has historically been characterized as a disease that affects young women of European ancestry, but recent studies indicate that the incidence and prevalence of the disease is much higher in Black and Hispanic populations than previously recognized. There is evidence that there is a more severe disease course in these populations. , but the intersection of genetic underpinnings and social determinants of health (SDOH) is poorly understood due to the lack of diversity in clinical research. Improving health disparities will involve multiple stakeholders in efforts to improve SDOH and raise awareness about research involvement and the importance of developing personalized health care plans to combat this disease.
Topics: Female; Humans; Ethnicity; Hispanic or Latino; Multiple Sclerosis; Black or African American
PubMed: 37980120
DOI: 10.1016/j.ncl.2023.06.005 -
Multiple Sclerosis and Related Disorders Dec 2023Persons with multiple sclerosis (MS) engage in less physical activity than the general population, and the disease manifestations and comorbidity conditions might... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Persons with multiple sclerosis (MS) engage in less physical activity than the general population, and the disease manifestations and comorbidity conditions might further predispose them toward sedentary behavior (SB) among this population. We performed a systematic review with meta-analysis of studies that compared SB in persons with MS and non-MS controls, and examined factors that may moderate the difference in SB between the two groups.
METHODS
We conducted a systematic search using PubMed, PsycINFO, Scopus, and CINAHL from inception up to August 2022, and identified studies that involved group comparison of SB outcomes between MS and non-MS controls. Effect sizes were calculated as standardized mean differences (SMDs) using Hedge's g. We generated a multilevel random-effects model for estimating an overall effect, and performed moderator analyses. Methodological quality was assessed using the Appraisal Tool for Cross-Sectional Studies (AXIS tool).
RESULTS
Eleven studies were included (1403 MS vs. 449 controls) and yielded 17 effects for meta-analysis. Results indicated an overall small, but significant effect (SMD [95% CI] = 0.27 [0.02, 0.53], p = 0.03) with significant heterogeneity (Q = 72.2, p < 0.01; I = 75.8%). There were larger effects when the MS sample had a higher proportion of females, or when SB was reported as percent sedentary time per day compared with other SB outcomes (p = 0.03 and 0.05, respectively). The included studies achieved fairly good quality (91.4%) using the AXIS tool.
CONCLUSIONS
The cumulative evidence supports that persons with MS engage in more SB than non-MS controls. Our findings may support the design of targeted behavioral change interventions for reducing SB and improving health and function in the MS population.
Topics: Female; Humans; Sedentary Behavior; Multiple Sclerosis; Cross-Sectional Studies; Exercise
PubMed: 37956522
DOI: 10.1016/j.msard.2023.105124 -
Magnetic Resonance Imaging Clinics of... May 2024Multiple advanced imaging methods for multiple sclerosis (MS) have been in investigation to identify new imaging biomarkers for early disease detection, predicting... (Review)
Review
Multiple advanced imaging methods for multiple sclerosis (MS) have been in investigation to identify new imaging biomarkers for early disease detection, predicting disease prognosis, and clinical trial endpoints. Multiple techniques probing different aspects of tissue microstructure (ie, advanced diffusion imaging, magnetization transfer, myelin water imaging, magnetic resonance spectroscopy, glymphatic imaging, and perfusion) support the notion that MS is a global disease with microstructural changes evident in normal-appearing white and gray matter. These global changes are likely better predictors of disability compared with lesion load alone. Emerging techniques in glymphatic and molecular imaging may improve understanding of pathophysiology and emerging treatments.
Topics: Humans; Brain; Magnetic Resonance Imaging; Multiple Sclerosis
PubMed: 38555138
DOI: 10.1016/j.mric.2024.01.002