Increase In Multiple Sclerosis Research Articles

Sodium Intensity Changes Differ Between Relaxation- and Density-Weighted MRI in Multiple Sclerosis.

Introduction: The source of Tissue Sodium Concentration (TSC) increase in Multiple Sclerosis (MS) remains unclear, and could be attributed to altered intracellular sodium concentration or tissue microstructure. This paper investigates sodium in MS using three new MRI sequences.Methods: Three sodium scans were acquired at 4.7 T from 30 patients (11 relapsing-remitting, 10 secondary-progressive, 9 primary-progressive) and 9 healthy controls including: Density-Weighted (NaDW), with very short 30° excitation for more accurate TSC measurement; Projection Acquisition with Coherent MAgNetization (NaPACMAN), designed for enhanced relaxation-based contrast; and Soft Inversion Recovery FLuid Attenuation (NaSIRFLA), developed to reduce fluid space contribution. Signal was measured in both lesions (n = 397) and normal appearing white matter (NAWM) relative to controls in the splenium of corpus callosum and the anterior and posterior limbs of internal capsule. Correlations with clinical and cognitive evaluations were tested over all MS patients.Results: Sodium intensity in MS lesions was elevated over control WM by a greater amount for NaPACMAN (75%) than NaDW (35%), the latter representing TSC. In contrast, NaSIRFLA exhibited lower intensity, but only for region specific analysis in the SCC (−7%). Sodium intensity in average MS NAWM was not significantly different than control WM for either of the three scans. NaSIRFLA in the average NAWM and specifically the posterior limb of internal capsules positively correlated with the Paced Auditory Serial Addition Test (PASAT).Discussion: Lower NaSIRFLA signal in lesions and ~2× greater NaPACMAN signal elevation over control WM than NaDW can be explained with a demyelination model that also includes edema. A NAWM demyelination model that includes tissue atrophy suggests no signal change for NaSIRFLA, and only slightly greater NAWM signal than control WM for both NaDW and NaPACMAN, reflecting experimental results. Models were derived from previous total and myelin water fraction study in MS with T2-relaxometry, and for the first time include sodium within the myelin water space. Reduced auditory processing association with lower signal on NaSIRFLA cannot be explained by greater demyelination and its modeled impact on the three sodium MRI sequences. Alternative explanations include intra- or extracellular sodium concentration change. Relaxation-weighted sodium MRI in combination with sodium-density MRI may help elucidate microstructural and metabolic changes in MS.

Is the sharp increasing trend of multiple sclerosis incidence real in Iran?

BackgroundSome epidemiologic studies have reported a sharp increase in multiple sclerosis (MS) incidence in different provinces in Iran. This report aimed to investigate more closely the increasing trend of MS incidence in the past 10 years in Iran.MethodsIn this longitudinal study, the data for all MS patients meeting the McDonald criteria were obtained from a national registry, coordinated by the Ministry of Health (MOH). Joinpoint (JP) regression was used for time trend analysis of MS incidence and determine the optimal number of significant joinpoints. Finally, an annual percentage change (APC) in MS incidence for each segment of the trend line was estimated with 95% confidence interval.ResultsThe mean age of the patients and the mean annual incidence rate of MS were 30.9 ± 1.1 and 5.3 ± 1.9 per 100,000 population, respectively. The overall incidence rate of MS had increased significantly from 2.14 in 2006 to its peak (7.5) in 2014, per 100,000 population (APC = 12%, P < 0.001). The first JP was observed in 2011 in both male and female groups. The overall APC in the first segment was 22.6% (17.2–28.2%, p < 0.01). Besides, the corresponding APC values for males and females were 22.1% (14.7–30%, p < 0.01) and 22.5% (17.5–27.8%, p < 0.01), respectively. After 2011, the MS incidence underwent a more or less decreasing trend in both genders.ConclusionContrary to previous studies, the MS incidence trend in Iran was rising just before 2011, and in the recent decade, Iran has a stable rate of MS cases.

Interpretation of Brain Volume Increase in Multiple Sclerosis.

A high variability of brain MRI volume change measurement renders challenging its interpretation in multiple sclerosis (MS). Occurrence and clinical relevance of observed apparent brain volume increase (BVI) in MS patients have not been investigated yet. The objective was to quantify the prevalence and factors associated with BVI. We examined 366 MS patients (2,317 scans) and 44 controls (132 scans). Volumetric analysis of brain volume changes was performed by SIENA and ScanView. BVI was defined as brain volume change >0%. We compared characteristics of patients with and without BVI. BVI was found in 26.3% (from 1,951) longitudinal scans (SIENA). If BVI occurred, a probability that BVI will be repeated consecutively more than or equal to two times was 15.9%. The repeated BVI was associated with clinical disease activity in 50% of cases. BVI was associated with shorter time and lower T2 lesion volume increase between two MRI scans, and higher normalized brain volume (all P<.0001). A proportion of scans with BVI was higher when analyzed by ScanView (35.3%) and in controls (36.4% by SIENA). BVI occurs in a great proportion of MR scans over short-term follow-up and is not associated with disease stabilization. Although BVI can be caused by several factors, the results indicate that measurement error may contribute to BVI in the majority of cases. Clinicians should be aware of the frequent occurrence of apparent BVI, interpret brain volume changes in MS patients with great caution, and use methods with precise quantification of brain volume changes.

The health burden of non-communicable neurological disorders in the USA between 1990 and 2017.

In this observational study, using the Global Burden of Disease and Risk Factors Study, we aimed to (i) report the magnitude of health loss due to non-communicable neurological disorders in the USA in 2017 by sex, age, years and States and (ii) to identify non-communicable neurological disorders attributable environmental, metabolic and behavioural risk factors. We provide estimates of the burden of non-communicable neurological disorders by reporting disability-adjusted life-years and their trends from 1990 to 2017 by age and sex in the USA. The non-communicable neurological disorders include migraines, tension-type headaches, multiple sclerosis, Alzheimer’s disease and other dementias, Parkinson’s disease, epilepsy, motor neuron diseases and other neurological disorders. In 2017, the global burdens of non-communicable neurological disorders were 1444.41 per 100 000, compared to the USA burden of 1574.0. Migraine was the leading age-standardized disability-adjusted life-years 704.7 per 100 000, with Alzheimer’s disease and other dementias (41.8.7), and epilepsy (123.8) taking the second and third places, respectively. Between 1990 and 2017, the age-standardized disability-adjusted life-years rates for aggregate non-communicable neurological disorders relative to all cause increased by 3.42%. More specifically, this value for motor neuron diseases, Parkinson’s disease and multiple sclerosis increase by 20.9%, 4.0%, 2.47%, 3.0% and 1.65%, respectively. In 2017, the age-standardized disability-adjusted life-years rates for the aggregate non-communicable neurological disorders was significantly higher in females than the males (1843.5 versus 1297.3 per 100 000), respectively. The age-standardized disability-adjusted life-years rates for migraine were the largest in both females (968.8) and males were (432.5) compared to other individual non-communicable neurological disorders. In the same year, the leading non-communicable neurological disorders age-standardized disability-adjusted life-years rates among children ≤9 was epilepsy (216.4 per 100 000). Among the adults aged 35–60 years, it was migraine (5792.0 per 100 000), and among the aged 65 and above was Alzheimer’s disease and other dementias (78 800.1 per 100 000). High body mass index, smoking, high fasting plasma glaucous and alcohol use were the attributable age-standardized disability-adjusted life-years risks for aggregate and individual non-communicable neurological disorders. Despite efforts to decrease the burden of non-communicable neurological disorders in the USA, they continue to burden the health of the population. Children are most vulnerable to epilepsy-related health burden, adolescents and young adults to migraine, and elderly to Alzheimer’s disease and other dementias and epilepsy. In all, the most vulnerable populations to non-communicable neurological disorders are females, young adults and the elderly.

Microbiome in Multiple Sclerosis; Where Are We, What We Know and Do Not Know.

An increase of multiple sclerosis (MS) incidence has been reported during the last decade, and this may be connected to environmental factors. This review article aims to encapsulate the current advances targeting the study of the gut–brain axis, which mediates the communication between the central nervous system and the gut microbiome. Clinical data arising from many research studies, which have assessed the effects of administered disease-modifying treatments in MS patients to the gut microbiome, are also recapitulated.

Оценка факторов риска развития рассеянного склероза в Республике Ингушетия

Currently the ubiquitous increase of multiple sclerosis (MS) prevalence is observed. The increase in number of patients with MS is marked also in the areas where MS prevalence was low previously, so the assessment of multiple sclerosis risk factors in populations with low multiple sclerosis risk is of a great value. There were no investigations of demyelinating disease epidemiology performed in the Republic of Ingushetia (RI) before. The purpose. To perform the clinical and epidemiological study of MS in RI; to study the factors, affecting the risk of MS development in RI population. Material and methods. We examined 73 patients (46 women and 27 men) with reliable MS (according to McDonald criteria, 2010, 2017). The investigation of risk factors of MS development was carried out by the method of analytical epidemiology «case-control». All respondents were inhabitants of RI, the pairs were comparable in age, gender and nationality. We studied serum concentration of vitamin D3 metabolite — 25(ОН)D3 by ELISA method. Results. Prevalence of NS in RI was 14.4 cases for 100 thousand of the population as of 1.01.2020. Among MS patients we revealed a higher frequency of contact with petrol and oil products (12 of 73 respondents vs 2 of 61 in groups of MS patients and control group respectively, р &lt; 0,05), and paints (15 of 73 respondents vs 2 of 61 in groups of MS patients and control group respectively, р &lt; 0,05), aged over 15 years old. Reliably more often than persons of control group MS patients have a case of surgical interventions, severe caries at the age over 15 years old (р &lt; 0,05), head injury at any age (р &lt; 0,05), tonsillitis, measles, rubella, parotitis occurred at the age before 7 years old (р &lt; 0,05) and herpetic infection at any age (р &lt; 0,05). According to the comparison of vitamin D3 metabolite — 25(ОН)D3 serum concentration parameters in MS patients of both sexes of RI population and control group we revealed a tendency to decrease of serum vitamin D level in MS patients; the differences in this feature in men with MS (15,15 (0,61) ng/ml) and men of control group (22,04 (8,0) ng/ml) were statistically reliable. Conclusion. The Republic of Ingushetia belongs to the areas of low-mild multiple sclerosis development risk, which is probably due to both demographic and geographical-climatic features. The external factors of MS development risk revealed in this research confirm the multifactor nature of the disease. Further investigations of the probable modifiability of these factors are of great importance.

Multiple Sclerosis Incidence and Prevalence Trends in the Province of Padua, Northeast Italy, 1965–2018

Background: Previous studies, dating back to the 1960s disclosed a progressive increase in multiple sclerosis (MS) incidence and prevalence in the Province of Padua. To further analyze whether this trend is the effect of the improved diagnostic procedures or is primarily related to a real increase risk of MS, we analyzed MS incidence and prevalence of the 5-year period 2011–2015. Methods: Patients with a diagnosis of MS or clinically isolated syndrome highly suggestive of MS were included in the study. All available sources of clinical and administrative information were evaluated. Mean annual incidence in the 5-year period 2011–2015 and the prevalence on December 31, 2015 were calculated. Results: The 2011–2015 mean incidence was 6.5/100,000/year, 7.9 for females, 4.1 for males. The overall prevalence was 182/100,000, 241 for females, 116 for males. Compared to the 2000–2009 period, mean age at onset, onset-diagnosis delay and F/M ratio did not significantly change. Since the 1960s, incidence and prevalence of MS linearly increased with no interposed plateau periods. Conclusions: MS incidence and prevalence further and significantly increased in the period 2011–2015. Our 1965–2015 data indicate a real increased risk of MS and stress a role of exogenous factors in MS susceptibility.

Is There Any Relevance Between Serum Heavy Metal Concentration and BBB Leakage in Multiple Sclerosis Patients?

Sharp increase in multiple sclerosis (MS) incidence rate has been observed in Iranian people. In addition, it has been suggested that increased S100B level may be useful as an indicative factor of blood-brain barrier disruption. The propose of this study was to measuring blood arsenic, lead, and cadmium concentration and serum S100B concentration in a group of healthy and multiple sclerosis patients in Tehran as the most polluted city in Iran. All subjects were interviewed regarding age, medical history, possible chemical exposure, acute or chronic diseases, smoking, and dietary habits. Blood heavy metal level was measured by an atomic absorption spectrometer (Varian model 220-Z) conjugated with a graphite furnace atomizer (GTA-110). Also, a serum S100B protein concentration was determined using a commercial ELISA kit. It was observed that all male subjects had higher blood metal level in comparison with healthy controls. Also, MS patients had higher arsenic and cadmium blood concentration in comparison with healthy individuals. Regarding the S100B concentration, it was observed that it had a significant relationship with smoking habit (P value = 0.0001). In addition, arsenic had a greater correlation (63%) with increased serum S100B biomarker level among other elements. BBB leakage was higher in multiple sclerosis than in healthy subjects due to increased S100B release. In addition with regard to the heavy metal exposure especially arsenic and cadmium, these are associated with an increased BBB disruption and it is possible to play a crucial role as a developing agent of multiple sclerosis.

We're on a road to nowhere: Culture and adaptation to the environment are driving human evolution, but the destination of this journey is unpredictable.

It is tempting to believe that humans, owing to their technological prowess, have elevated themselves above the laws of biology and escaped natural selection. Indeed, some think that humans have stopped evolving at all. Another view holds that Homo sapiens has not isolated itself from the influences of the physical and biological world but that our species is just a special, extreme case of niche constructors. This view is based on the so‐called Niche Construction Theory, a development within evolutionary biology to describe how humans—and many other organisms—modify their environment—or niche—in a way that alters environmental pressures and therefore natural selection. Thus, rather adapting to a pre‐existing environment, “organisms drive environmental change and organism‐modified environments subsequently select organisms” (https://synergy.st-andrews.ac.uk/niche/niche-construction-and-evolution/) (Box 1). ### Culture‐driven evolution “[All] organisms adapt to their environment, and in humans much of our environment is defined by our culture. Hence, cultural change can actually spur on adaptive evolution in humans”, wrote evolutionary biologist Alan Templeton at Washington University in St. Louis, MO, USA. [1]. Following this argument, culture, social learning and technology have not replaced biological adaptation. Rather, human evolution is driven by the environmental conditions we created ourselves through culture, a process that has been accelerating since the beginning of agriculture and urban civilization. In other words, cultural niche construction is a major cause of recent human evolution. However, there are other factors than natural selection, such as genetic drift and gene flow, that influence human evolution [1]. Nonetheless, even the effects of these random, non‐adaptive forces on human genetic variation are somehow altered by cultural trends, namely increased urbanization and greater mobility. As a consequence, drift is diminishing and gene flow is increasing, a process that would eventually culminate into a single “species‐wide” gene pool characterized by high levels of genetic variation. > [C]ulture, …

Hormonal contraception and the development of autoimmunity: A review of the literature.

Hormonal contraceptives (HCs), such as the "pill," Norplant, and vaginal rings, are very potent hormones that have effects on the immune system, which is made up of white blood cells and lymph nodes and normally defends the body against invading bacteria, viruses and parasites. This review looked at the association of HC use to the development of autoimmune diseases, where the immune system turns against the body and causes damage to organs. There is good evidence that HC use is associated with an increased risk of several serious autoimmune diseases such as Crohn's disease (which causes inflammation of the bowels), Lupus (which causes inflammation in many organs), and interstitial cystitis (which causes inflammation in the bladder). Several other rarer autoimmune diseases are also linked to HC use. People contemplating the use of HCs should be informed of these risks.

Central Nervous System Penetration for Small Molecule Therapeutic Agents Does Not Increase in Multiple Sclerosis- and Alzheimer's Disease-Related Animal Models Despite Reported Blood-Brain Barrier Disruption

Therapy for central nervous system (CNS) diseases requires drugs that can cross the blood-brain barrier (BBB). BBB disruption has been reported in patients with multiple sclerosis (MS) and Alzheimer's disease (AD) and the related animal models as evidenced by increased infiltration of inflammatory cells or increased staining of Igs in the central nervous system. Although CNS penetration of therapeutic agents under pathological conditions has rarely been investigated, it is commonly assumed that BBB disruption may lead to enhanced CNS penetration and also provide a "window of opportunity" through which drugs that do not normally cross BBB are able to do so. In this article, we have compared brain penetration of eight small molecules in naive animals and experimental autoimmune encephalomyelitis (EAE) mice, streptozotocin-induced mice, and TASTPM transgenic mice. The tool compounds are lipophilic transcellular drugs [GlaxoSmithKline (GSK)-A, GSK-B, GSK-C, and naproxen], lipophilic P-glycoprotein (P-gp) substrates (amprenavir and loperamide), and hydrophilic paracellular compounds (sodium fluorescein and atenolol). Our data showed that rate and extent of CNS penetration for lipophilic transcellular drugs and P-gp substrates are similar in naive and all tested animal models. The brain penetration for paracellular drugs in EAE mice is transiently increased but similar to that in naive mice at steady state. Our data suggest that, despite reported BBB disruption, CNS penetration for small molecule therapeutic agents does not increase in MS- and AD-related animal models.

Hygiene hypothesis: Innate immunity, malaria and multiple sclerosis

The establishment of new hygienic conditions plays a role in the appearance of autoimmunity in "westernalised" countries. Consistently, but still unconvincingly, several epidemiological and immunogenetic evidences link the disappearance of malaria with the increase of multiple sclerosis (MS) in Sardinia, insular Italy. To this purpose, we have made an attempt to build a relationship between malaria disappearance and MS under the light of the hygiene hypothesis. This relationship has taken into account the MS frequency increase soon after malaria eradication in Sardinia, the present malaria endemism in Africa, the innate immune system activity here represented by Chitotriosidase (Chit), an hydrolytic enzyme produced by macrophages, and an unproductive polymorphism of Chit gene (CHIT1) as a measure of the genetic weight of Plasmodium-related immunity in these populations. Data were derived from both experimental results specifically designed for this study and other data obtained from the available literature. The experimental and the hystorical-epidemiological findings concur to indicate that whilst in Africa CHIT1 mutation is rare and MS incidence is very low due to unmodified parasitic influence and hygienic conditions, in Sardinia a relationships between CHIT1 mutation, plasma Chit activity and MS prevalence rate is detected, even to a higher extent compared to Sicily, area at former lower rate of malaria endemy. Upon such a basis, we have found convincing argumentations that, at least in part, MS has increased over the last four decades in Sardinia also because of the eradication of malaria, 50 years ago. This infectious disease that run for centuries in Sardinia, besides well documented enzyme deficiencies and red cell pathologies, have left an abnormal macrophage reactivity against Plasmodium falciparum. As a result, some Sardinian individuals secrete abnormally high levels of mediators of the innate immunity, relics of former protective anti-malaria infection, in response to new environmental factors. Therefore, MS, an immune-conditioned pathology of the central nervous system has been subject to an unexplained epidemiological increase in the last few decades in Sardinia because cells of the innate immune system, immuno-genetically selected over the centuries in response to widespread P. falciparum malaria, have kept the tendency to over-respond to triggering factors even after the disappearance of malaria. This hypothesis may have an influence in re-directing clinicians toward a innate immunity-based rather than an antigen specific-based new MS therapies.

Leptin increase in multiple sclerosis associates with reduced number of CD4(+)CD25+ regulatory T cells.

We analyzed the serum and cerebrospinal fluid (CSF) leptin secretion and the interaction between serum leptin and CD4(+)CD25+ regulatory T cells (T(Regs)) in naive-to-therapy relapsing-remitting multiple sclerosis (RRMS) patients. Leptin production was significantly increased in both serum and CSF of RRMS patients and correlated with IFN-gamma secretion in the CSF. T cell lines against human myelin basic protein (hMBP) produced immunoreactive leptin and up-regulated the expression of the leptin receptor (ObR) after activation with hMBP. Treatment with either anti-leptin or anti-leptin-receptor neutralizing antibodies inhibited in vitro proliferation in response to hMBP. Interestingly, in the RRMS patients, an inverse correlation between serum leptin and percentage of circulating T(Regs) was also observed. To better analyze the finding, we enumerated T(Regs) in leptin-deficient (ob/ob) and leptin-receptor-deficient (db/db) mice and observed the significant increase in T(Regs). Moreover, treatment of WT mice with soluble ObR fusion protein (ObR:Fc) increased the percentage of T(Regs) and ameliorated the clinical course and progression of disease in proteolipid protein peptide (PLP(139-151))-induced relapsing-experimental autoimmune encephalomyelitis (R-EAE), an animal model of RRMS. These findings show an inverse relationship between leptin secretion and the frequency of T(Regs) in RRMS and may have implications for the pathogenesis of and therapy for multiple sclerosis.

Hyaluronan in human cerebrospinal fluid.

We studied the concentration of hyaluronan in cerebrospinal fluid (CSF) in various diseases and attempted to define its reference interval. A radioassay utilizing cartilage proteins with affinity for hyaluronan was used in determining the concentration of 200 lumbar and 27 ventricular CSF specimens and 11 brain cyst fluids. Molecular weight distributions were determined by gel chromatography and localization in brain tissue by histochemistry. The hyaluronan level of lumbar CSF showed an increase with age; comparatively healthy children had (mean +/- SD) 50 +/- 41 micrograms/L (n = 40) and adults 166 +/- 77 micrograms/L (n = 9); i.e. significantly different values. The highest level was recorded in a patient with meningitis (> 8000 micrograms/L). More than 4000 micrograms/ L was noted in a patient with tumour metastasis in the cerebellum. Significantly elevated levels were especially found with spinal stenosis, head injury and cerebral infarction, but also in inflammatory medical disorders, hydrocephalus and encephalitis. We found no significant increase in multiple sclerosis and some other neurological diseases. Ventricular CSF of adults contained significantly less hyaluronan (53 +/- 73 micrograms/L; n = 16) than lumbar CSF. Hyaluronan in cyst fluids varied from 31 to 25,000 micrograms/L. Weight average molecular weight of hyaluronan in CSF was 2.9-3.0 x 10(5) and in brain tumour cyst fluid 2.4 x 10(6). In search for the origin of hyaluronan in CSF it was found that its concentration in the choroid plexus and leptomeninges was low, but that hyaluronan was accumulated in the superficial layer of the cerebral cortex. Continued screening for hyaluronan in CSF may be valuable in cases of inflammatory diseases, tumours and obstruction to CSF flow.

Some comments on the occurrence of multiple sclerosis in the Faroe Islands.

Some factors which might be related to the marked increase in multiple sclerosis in the Faroe Islands in mid-century were studied. Of these, only the occupation by British troops in World War II was found to be significant. A vague relationship with industrial changes earlier in the century was also found. These findings are discussed with caution with respect to the close association between population on the one hand and all features tested as well as multiple sclerosis on the other.