Multiple sclerosis (MS) is more prevalent in women than in men. The sex of the patient, and pregnancy, are reported to be associated with the clinical features of MS. The mechanism of this is ...unclear.
This review summarizes data about sex differences in MS and the role of pregnancy. Possible mechanisms for the effects of sex and pregnancy are summarized, and practical suggestions for addressing these issues are provided.
There is considerable interdependence of the variables that are associated with MS. Men have a worse outcome of MS, and this could be due to the same factors that lead to greater incidence of neurodegenerative disease in men. The possible role of parity on the long-term outcome of MS is of interest. Future studies that look at the mechanisms of the effects of the sex of the patient on the outcome of MS are required. However, there are some actions that can be taken without further research. We can concentrate on public health measures that address the modifiable risk factors for MS and ensure that disease is controlled in women who intend to become pregnant and use appropriate disease modifying agents during pregnancy.
To allow early diagnosis and monitoring of disease progression, there is a need for biomarkers in amyotrophic lateral sclerosis (ALS). Neurofilaments (NF) are emerging protein biomarkers in other ...neurological diseases, and are of possible use in ALS.
The aim of this study is to evaluate the utility of NF levels as blood or cerebrospinal fluid (CSF) biomarker in patients with ALS.
A systematic search of Pubmed, Embase and Scopus was performed. Methodological quality assessment was applied to refine the final search results. Meta-analysis of the data was performed.
Level of NF heavy chain and light chains were significantly elevated in the CSF of ALS patients compared to healthy controls/controls without parenchymal central nervous system (CNS) involvement and ALS mimic disease patients. NF light chain level in CSF was higher in ALS patients than in neurological patients with CNS involvement (SMD = 1.352, P = 0.01). NF light chain concentration in blood was higher in ALS patients than healthy controls/controls without CNS involvement (SMD = 1.448, P<0.0001). NF heavy chain levels in CSF were negatively correlated disease duration and ALSFRS-R ((r = -0.447, P<0.0001; r = -0.486, P<0.0001). NF light chain levels in CSF were negatively correlated with disease duration (r = -0.273, P = 0.011).
NF heavy and light chain levels have potential use as a marker of neural degeneration in ALS, but are not specific for the disease, and are more likely to be used as measures of disease progression.
Background and purpose
Weight loss in patients with amyotrophic lateral sclerosis (ALS) is associated with faster disease progression and shorter survival. Decreased hypothalamic volume is proposed ...to contribute to weight loss due to loss of appetite and/or hypermetabolism. We aimed to investigate the relationship between hypothalamic volume and body mass index (BMI) in ALS and Alzheimer's disease (AD), and the associations of hypothalamic volume with weight loss, appetite, metabolism and survival in patients with ALS.
Methods
We compared hypothalamic volumes from magnetic resonance imaging scans with BMI for patients with ALS (n = 42), patients with AD (n = 167) and non‐neurodegenerative disease controls (n = 527). Hypothalamic volumes from patients with ALS were correlated with measures of appetite and metabolism, and change in anthropomorphic measures and disease outcomes.
Results
Lower hypothalamic volume was associated with lower and higher BMI in ALS (quadratic association; probability of direction = 0.96). This was not observed in AD patients or controls. Hypothalamic volume was not associated with loss of appetite (p = 0.58) or hypermetabolism (p = 0.49). Patients with lower BMI and lower hypothalamic volume tended to lose weight (p = 0.08) and fat mass (p = 0.06) over the course of their disease, and presented with an increased risk of earlier death (hazard ratio HR 3.16, p = 0.03). Lower hypothalamic volume alone trended for greater risk of earlier death (HR 2.61, p = 0.07).
Conclusion
These observations suggest that lower hypothalamic volume in ALS contributes to positive and negative energy balance, and is not universally associated with loss of appetite or hypermetabolism. Critically, lower hypothalamic volume with lower BMI was associated with weight loss and earlier death.
Background:
The history of multiple sclerosis (MS) is dominated by the discoveries of famous men. However, women would like to feel part of the story and to know that women have contributed to MS ...research.
Objective:
To identify women who contributed to the history of discovery in MS.
Method:
This was a personal survey from my knowledge of previous work.
Results:
There were no women participants in the early stages of MS research. However, since 1950 there are many women who have contributed to MS research. In the 20th century, there were famous women who contributed to the scientific fields that form the basis of MS research. In the 21st century, more women participate in MS research but studies suggest that they are under-represented in positions of prominence.
Conclusion:
Women have been part of the effort to understand MS, but are not well recognized.
Experimental autoimmune encephalomyelitis (EAE) can be induced in many animal strains by inoculation with central nervous system antigens and adjuvant or by the passive transfer of lymphocytes ...reactive with these antigens and is widely used as an animal model for multiple sclerosis (MS). There are reports that female sex and pregnancy affect EAE. Here we review the effects of biological sex and the effects of pregnancy on the clinical features (including disease susceptibility) and pathophysiology of EAE. We also review reports of the possible mechanisms underlying these differences. These include sex-related differences in the immune system and in the central nervous system, the effects of hormones and the sex chromosomes and molecules unique to pregnancy. We also review sex differences in the response to factors that can modify the course of EAE. Our conclusion is that the effects of biological sex in EAE vary amongst animal models and should not be widely extrapolated. In EAE, it is therefore essential that studies looking at the effects of biological sex or pregnancy give full information about the model that is used (i.e. animal strain, sex, the inducing antigen, timing of EAE induction in relation to pregnancy, etc.). In addition, it would be preferable if more than one EAE model were used, to show if any observed effects are generalizable. This is clearly a field that requires further work. However, understanding of the mechanisms of sex differences could lead to greater understanding of EAE, and suggest possible therapies for MS.
Neurotransmitters and neurochemicals can act on lymphocytes by binding to receptors expressed by lymphocytes. This review describes lymphocyte expression of receptors for a selection of ...neurotransmitters and neurochemicals, the anatomical locations where lymphocytes can interact with neurotransmitters, and the effects of the neurotransmitters on lymphocyte function. Implications for health and disease are also discussed.
•Lymphocytes express receptors for neurotransmitters.•Lymphocytes produce and respond to neurotransmitters.•Some neurotransmitters are immunosuppressive, others stimulate immunity.•Therapies directed at neurotransmitters could potentially affect the immune system.
Many pathogenetic mechanisms have been proposed for amyotrophic lateral sclerosis (ALS). Recently, there have been emerging suggestions of a possible role for the gut microbiota. Gut microbiota have ...a range of functions and could influence ALS by several mechanisms. Here, we review the possible role of gut-derived neurotoxins/excitotoxins. We review the evidence of gut symptoms and gut dysbiosis in ALS. We then examine a possible role for gut-derived toxins by reviewing the evidence that these molecules are toxic to the central nervous system, evidence of their association with ALS, the existence of biochemical pathways by which these molecules could be produced by the gut microbiota and existence of mechanisms of transport from the gut to the blood and brain. We then present evidence that there are increased levels of these toxins in the blood of some ALS patients. We review the effects of therapies that attempt to alter the gut microbiota or ameliorate the biochemical effects of gut toxins. It is possible that gut dysbiosis contributes to elevated levels of toxins and that these could potentially contribute to ALS pathogenesis, but more work is required.
Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease that is defined by loss of upper and lower motor neurons, associated with accumulation of protein aggregates in cells. There ...is also pathology in extra-motor areas of the brain, Possible causes of cell death include failure to deal with the aggregated proteins, glutamate toxicity and mitochondrial failure. ALS also involves abnormalities of metabolism and the immune system, including neuroinflammation in the brain and spinal cord. Strikingly, there are also abnormalities of the peripheral immune system, with alterations of T lymphocytes, monocytes, complement and cytokines in the peripheral blood of patients with ALS. The precise contribution of the peripheral immune system in ALS pathogenesis is an active area of research. Although some trials of immunomodulatory agents have been negative, there is strong preclinical evidence of benefit from immune modulation and further trials are currently underway. Here, we review the emerging evidence implicating peripheral immune alterations contributing to ALS, and their potential as future therapeutic targets for clinical intervention.
Guillain Barré syndrome (GBS) and its variants, and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP and its variants, are regarded as immune mediated neuropathies. Unlike in many ...autoimmune disorders, GBS and CIDP are more common in males than females. Sex is not a clear predictor of outcome. Experimental autoimmune neuritis (EAN) is an animal model of these diseases, but there are no studies of the effects of sex in EAN. The pathogenesis of GBS and CIDP involves immune response to non-protein antigens, antigen presentation through non-conventional T cells and, in CIDP with nodopathy, IgG4 antibody responses to antigens. There are some reported sex differences in some of these elements of the immune system and we speculate that these sex differences could contribute to the male predominance of these diseases, and suggest that sex differences in peripheral nerves is a topic worthy of further study.
Guillain‐Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are thought to be autoimmune diseases. There have been many attempts to find a human leukocyte ...antigen (HLA) association with GBS and CIDP with little success. There have been studies of other plausible genes in GBS and CIDP and the role of these genes in GBS and CIDP and the data from these genetic studies is reviewed. Some of the genes that have been studied are immune related and some others have nervous system effects. The studies are limited by small numbers. Some of the genes show association with disease severity rather than disease susceptibility. The need for more detailed molecular studies of the role of HLA molecules and the need for modern genetic approaches to GBS and CIDP are explained.
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