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Background: There is increasing need for evidence-based data on reproduction for women with multiple sclerosis (MS). First-trimester (first 13 weeks) miscarriages are relatively common in the general population. It is therefore important to have information on the frequency with which this occurs in women with MS. Methods: The Canadian Multiple Sclerosis Pregnancy Study (CANPREG-MS) is a prospective study on women with MS who are pregnant or actively trying to conceive. As far as we are aware, this is the first study on miscarriages for this population that takes into account each woman's entire pregnancy history (i.e. before and after the MS diagnosis as well as during enrollment in CANPREG-MS). Results: There were 208 pregnancies during the study and 36 resulted in first-trimester miscarriage for a rate of 17.31%, within the expected range of 15%–20% for the general population. Conclusions: CANPREG-MS provides real world data that there does not appear to be an increase in first-trimester miscarriages for women with MS. This information will be helpful to women with MS and their healthcare providers. [ABSTRACT FROM AUTHOR]

Objective: The objective of this prospective "real world" study is to gain insight into the different "roads to conception" that women with MS take as part of the prospective Canadian Multiple Sclerosis Pregnancy Study (CANPREG-MS). Methods: Participants are women with MS who are planning a pregnancy. Data cut-off for analyses was April 30, 2020. Results: We believe this is the first prospective National study of women with MS planning pregnancies. The data are for the first 44 women enrolled of whom 26 achieved pregnancy by cut-off date. Seven women used assisted reproductive technologies (ARTs); 6 stopped disease modifying therapy (DMT) against their neurologists' recommendations; 6 had an interruption(s) in trying to conceive due to MS relapses, MRI-detected inflammation, or limited "windows of opportunity" between DMT courses. Conclusion: The study illustrates the roads that women take to conception, even if they are on the same therapy and have similar clinical expression of MS. Advice given by treating neurologists on washout periods show discrepancies. This paper highlights the real problem that there is no definitive, international consensus on managing these women due to the lack of "real world" data and thus the goal of CANPREG-MS is to provide such real world data. [ABSTRACT FROM AUTHOR]

Abstract Background There is a strong maternal parent-of-origin effect in determining susceptibility to multiple sclerosis (MS). One hypothesis is that an abnormal intrauterine milieu leading to impaired fetal development could plausibly also result in increased susceptibility to MS. A possible marker for this intrauterine insult is the presence of a non-fatal congenital anomaly. Methods We investigated whether or not congenital anomalies are associated with MS in a population-based cohort. We identified 7063 MS index cases and 2655 spousal controls with congenital anomaly information from the Canadian Collaborative Project on Genetic Susceptibility to MS (CCPGSMS). Results The frequency of congential anomalies were compared between index cases and controls. No significant differences were found. Conclusions Congenital anomalies thus do not appear to be associated with MS. However, we did not have complete data on types and severity of congenital anomalies or on maternal birth history and thus this study should be regarded as preliminary.

Elucidation of distinct T-cell subsets involved in multiple sclerosis immune-pathophysiology continues to be of considerable interest since an ultimate goal is to more selectively target the aberrant immune response operating in individual patients. While abnormalities of both effector (Teff) and regulatory (Treg) T cells have been reported in patients with multiple sclerosis, prior studies have mostly assessed average abnormalities in either limb of the immune response, rather than both at the same time, which limits the ability to evaluate the balance between effectors and regulators operating in the same patient. Assessing both phenotypic and functional responses of Teffs and Tregs has also proven important. In studies of adults with multiple sclerosis, in whom biological disease onset likely started many years prior to the immune assessments, an added challenge for any reported abnormality is whether the abnormality indeed contributes to the disease (and hence of interest to target therapeutically) or merely develops consequent to inflammatory injury (in which case efforts to develop targeted therapies are unlikely to be beneficial). Paediatric-onset multiple sclerosis, though rare, offers a unique window into early disease mechanisms. Here, we carried out a comprehensive integrated study, simultaneously assessing phenotype and functional responses of both effector and regulatory T cells in the same children with multiple sclerosis, monophasic inflammatory CNS disorders, and healthy controls, recruited as part of the multicentre prospective Canadian Pediatric Demyelinating Disease Study (CPDDS). Stringent standard operating procedures were developed and uniformly applied to procure, process and subsequently analyse peripheral blood cells using rigorously applied multi-parametric flow cytometry panels and miniaturized functional assays validated for use with cryopreserved cells. We found abnormally increased frequencies and exaggerated pro-inflammatory responses of CD8+CD161highTCR-Vα7.2+ MAIT T cells and CD4+CCR2+CCR5+ Teffs in paediatric-onset multiple sclerosis, compared to both control groups. CD4+CD25hiCD127lowFOXP3+ Tregs of children with multiple sclerosis exhibited deficient suppressive capacity, including diminished capacity to suppress disease-implicated Teffs. In turn, the implicated Teffs of multiple sclerosis patients were relatively resistant to suppression by normal Tregs. An abnormal Teff/Treg ratio at the individual child level best distinguished multiple sclerosis children from controls. We implicate abnormalities in both frequencies and functional responses of distinct pro-inflammatory CD4 and CD8 T cell subsets, as well as Treg function, in paediatric-onset multiple sclerosis, and suggest that mechanisms contributing to early multiple sclerosis development differ across individuals, reflecting an excess abnormality in either Teff or Treg limbs of the T cell response, or a combination of lesser abnormalities in both limbs. [ABSTRACT FROM AUTHOR]

The article discusses a study regarding the female puberty-enhanced risk of multiple sclerosis (MS) in children and central nervous system (CNS) autoimmunity in mice. Topics discussed include experimental autoimmune encephalomyelitis (EAE), acquired demyelinating syndromes (ADS), and the use of brain magnetic resonance imaging (MRI).

The article offers information about the diagnosis and treatment of dementia. It also offers practical guidance to physicians on risk assessment and primary prevention of Alzheimer's disease. Modifiable factors for Alzheimer's disease include hyperlipidemia, hypertension, and environmental exposures. Primary prevention of Alzheimer's disease includes regulating vascular risk factors, and weak or insufficient evidence for control of lifestyle factors and prescription of medicines. Avoidance of estrogens and high dosages of vitamin A are also included.

Background: There is a strong maternal parent-of-origin effect in determining susceptibility to multiple sclerosis (MS). One hypothesis is that an abnormal intrauterine milieu leading to impaired fetal development could plausibly also result in increased susceptibility to MS. A possible marker for this intrauterine insult is the presence of a nonfatal congenital anomaly. Methods: We investigated whether or not congenital anomalies are associated with MS in a population-based cohort. We identified 7063 MS index cases and 2655 spousal controls with congenital anomaly information from the Canadian Collaborative Project on Genetic Susceptibility to MS (CCPGSMS). Results: The frequency of congential anomalies were compared between index cases and controls. No significant differences were found. Conclusions: Congenital anomalies thus do not appear to be associated with MS. However, we did not have complete data on types and severity of congenital anomalies or on maternal birth history and thus this study should be regarded as preliminary. [ABSTRACT FROM AUTHOR]