Multiple sclerosis in Morocco: Epidemiological, clinical, and therapeutic profile.

OBJECTIVE: This study aims to describe the clinical, therapeutic, and epidemiological profiles of MS patients in Morocco. METHODS: This descriptive study involved 170 patients representing four Morocco regions. We collected the data using an electronic survey. RESULTS: The results show female dominance in patients with MS. Besides, most patients present with relapsing-remitting MS (RRMS). The main clinical symptoms reported by patients are fatigue, cognitive issues, spasticity, bowel or bladder complaints, and visual issues. Furthermore, the findings show that almost half of the patients use Interferon bêta-1a and azathioprine as disease-modifying therapies; 60.5 % use traditional and complementary medicine, of which 30.6 % use cupping, 30 % recite the Holy Quran, and 28.2 % use apitherapy. The findings show that there is a statistically significant relationship between specific MS factors such as professional activity (p = 0.0071), degree of satisfaction with treatment (p = 0.005), stress (p = 0.014), and the frequency of relapses. CONCLUSIONS: In addition to DMT, patients also use traditional and complementary medicine. There is also a relationship between some epidemiological characteristics and the frequency of relapses in patients with MS.

Performance of administrative databases for identifying individuals with multiple sclerosis.

Administrative databases are an alternative to disease registries as a research tool to study multiple sclerosis. However, they are not initially designed to fulfill research purposes. Therefore, an evaluation of their performance is necessary. Our objective was to assess the performance of the French administrative database comprising hospital discharge records and national health insurance databases in identifying individuals with multiple sclerosis, in comparison with a registry that exhaustively compiles resident multiple sclerosis cases in Lorraine, northeastern France, as reference. We recorded all individuals residing in the Lorraine region who were identified by the administrative database or the registry as having multiple sclerosis from 2011 to 2016. We calculated the Matthews correlation coefficient and other concordance indicators. For identifying individuals with multiple sclerosis, the Matthews correlation coefficient by the administrative database was 0.79 (95% CI 0.78-0.80), reflecting moderate performance. The mean time to identification was 5.5 years earlier with the registry than the administrative database. Administrative databases, although useful to study multiple sclerosis, should be used with caution because results of studies based on them may be biased. Our study highlights the value of regional registries that allow for a more exhaustive and rapid identification of cases.

Health Effects of Vitamin D Supplementation: Lessons Learned From Randomized Controlled Trials and Mendelian Randomization Studies.

Vitamin D plays an important role in calcium homeostasis and many cellular processes. Although vitamin D supplements are widely recommended for community-dwelling adults, definitive data on whether these supplements benefit clinically important skeletal and extraskeletal outcomes have been conflicting. Although observational studies on effects of vitamin D on musculoskeletal and extraskeletal outcomes may be confounded by reverse causation, randomized controlled studies (RCTs) and Mendelian randomization (MR) studies can help to elucidate causation. In this review, we summarize the recent findings from large RCTs and/or MR studies of vitamin D on bone health and risk of fractures, falls, cancer, and cardiovascular disease, disorders of the immune system, multiple sclerosis, and mortality in community-dwelling adults. The primary analyses indicate that vitamin D supplementation does not decrease bone loss, fractures, falls, cancer incidence, hypertension, or cardiovascular risk in generally healthy populations. Large RCTs and meta-analyses suggest an effect of supplemental vitamin D on cancer mortality. The existence of extraskeletal benefits of vitamin D supplementations are best documented for the immune system especially in people with poor vitamin D status, autoimmune diseases, and multiple sclerosis. Accumulating evidence indicates that vitamin D may reduce all-cause mortality. These findings, in mostly vitamin D-replete populations, do not apply to older adults in residential communities or adults with vitamin D deficiency or osteoporosis. The focus of vitamin D supplementation should shift from widespread use in generally healthy populations to targeted vitamin D supplementation in select individuals, good nutritional approaches, and elimination of vitamin D deficiency globally. © 2023 American Society for Bone and Mineral Research (ASBMR).

Investigating the potential link between lunar cycle and multiple sclerosis relapses: a call for further studies.

Multiple sclerosis (MS) is a debilitating disease that causes inflammation of the central nervous system, resulting in myelin damage and axon degeneration. Although the cause of MS remains unknown, various factors such as sex, latitude, sun exposure, serum vitamin D levels, Epstein Barr Virus infection, diet, microbiota and ethnicity are being studied for their potential roles in the development of the disease. While chronobiological factors such as circadian rhythm and seasonality have been explored for their potential influence on the onset, exacerbation, and/or relapses of MS, the potential influence of the lunar cycle on MS has yet to be studied. Therefore, the authors of this letter call for future studies to investigate the possible effects of the lunar cycle on MS activity and course, given evidence suggesting that the lunar cycle may affect sleep, fatigue, melatonin secretion, and mood state in humans. A deeper understanding of the chronobiology of MS could have practical implications for the development of chronotherapeutic strategies and the prevention or mitigation of MS relapses, potentially improving the quality of life of MS patients.

A case-control study of drinking beverages and the risk of multiple sclerosis in Iran.

BACKGROUND: There is no study in the world on the relationship between consuming black and green tea as beverages containing polyphenols and the risk of MS. This study aimed to determine the association between the consumption of green and black tea, coffee, non-alcoholic beer, milk, fruit juices and carbonated beverages with the risk of MS. METHODS AND MATERIALS: This case-control study was performed on 150 patients with MS and 300 healthy individuals as a control group among patients who were referred to the ophthalmology ward of a referral hospital in Ahvaz with the groups matching for age. The data collection tool was a researcher-made questionnaire including demographic information and beverage consumption. Analysis was performed using univariate and multiple logistic regression models. RESULTS: The mean age of patients at the time of diagnosis was 38.55 ± 8.88 years. The results showed that drinking milk (OR = 5.46), natural juice (OR = 2.49), and carbonated beverages (OR = 16.17) were associated with an increased chance of developing MS. However, drinking non-alcoholic beer (OR = 0.48), black tea (OR = 0.20), green tea (OR = 0.29) and coffee (OR = 0.07) were associated with a reduced chance of developing MS. CONCLUSION: The results show that drinking black and green tea, non-alcoholic beer, and coffee are associated with a decrease in the chance of developing MS. The results of this study can be used to design interventional research and to change people's lifestyles to prevent MS.

Melatonin and vitamin D, two sides of the same coin, better to land on its edge to improve multiple sclerosis.

Previous studies revealed a latitudinal gradient of multiple sclerosis (MS) prevalence, increasing by moving from the equator to the poles. The duration and quality of an individual's exposure to sunlight vary with latitude. Skin exposure to sunlight activates vitamin D synthesis, while light absence, as perceived by the eyes, activates melatonin synthesis in the pineal gland. Vitamin D or melatonin deficiency/insufficiency or overdose can occur at any latitude due to specific lifestyles and diets. Moving away from the equator, especially beyond 37°, decreases vitamin D while raising melatonin. Furthermore, melatonin synthesis increases in cold habitats like northern countries. Since melatonin's beneficial role was shown in MS, it is expected that northern countries whose individuals have higher endogenous melatonin should show a lower MS prevalence; however, these are ranked with the highest scores. In addition, countries like the United States and Canada have uncontrolled over-the-counter usage. In high latitudes, vitamin D deficiency and a higher MS prevalence persist even though vitamin D is typically compensated for by supplementation and not sunlight. Recently, we found that prolonged darkness increased MS melatonin levels, mimicking the long-term increase in northern countries. This caused a reduction in cortisol and increased infiltration, inflammation, and demyelination, which were all rescued by constant light therapy. In this review, we explain melatonin and vitamin D's possible roles in MS prevalence. The possible causes in northern countries are then discussed. Finally, we suggest strategies to treat MS by manipulating vitamin D and melatonin, preferably with sunlight or darkness, not supplements.

Vitamin D genetic risk scores in multiple sclerosis.

BACKGROUND: Low serum 25(OH)D3 (vD) is an environmental risk factor for multiple sclerosis (MS). Lower vD levels during early disease may be associated with long-term disability. Determinants of serum vD levels in healthy individuals include supplementation behaviour and genetic factors. These determinants have been less well studied in people with MS (pwMS). METHODS: We developed a vD-weighted genetic risk score (GRS) and validated this in 373,357 UK Biobank participants without MS. We measured serum 25(OH)D3 and genotyped six vD-associated SNPs (rs12785878, rs10741657, rs17216707, rs10745742, rs8018720, rs2282679) in a cohort of pwMS (n = 315) with age and geographically matched controls (n = 232). We then assessed predictors of serum vD concentration in this cohort. RESULTS: The GRS was strongly associated with vD status in the Biobank cohort (p < 2 × 10-16). vD supplementation, having MS, lower BMI, increased age and supplementation dose were associated with higher vD levels (false discovery rate, FDR < 5%). In multivariable models adjusting for supplementation, BMI, age, sex, and MS status, the GRS was strongly associated with vD level (p = 0.004), but not in those who supplemented (p = 0.47). CONCLUSIONS: Our findings suggest that vD supplementation is the major determinant of vD level in pwMS, with genetic determinants playing a far smaller role.

Complementary and alternative medicine in multiple sclerosis: a questionnaire-based study.

AIM OF THE STUDY: To assess the prevalence and characteristics of complementary and alternative medicine (CAM) use among multiple sclerosis (MS) patients in Poland. CLINICAL RATIONALE FOR THE STUDY: Multiple sclerosis (MS) is a chronic, progressive and disabling neurological disease with significant impact on quality of life. Although the efficacy and safety of complementary and alternative medicine (CAM) has not been scientifically confirmed, many patients use CAM as a complement or an alternative to conventional therapy. MATERIAL AND METHODS: Data was collected via a self-designed survey consisting of 33 questions. The questionnaire was distributed among MS patients hospitalised during 2016 in the MS Unit at the Department of Neurology, Medical University of Warsaw, Poland. The study group consisted of 75 patients (47 females, 28 males, mean age 44.6 ± 12.5 years) with clinically defined MS. RESULTS: According to the questionnaire, 48 patients (64%) had used CAM at least once. Most of the patients declared that CAM had a possible (58%) or a marked (43.7%) positive effect. 61.4% of CAM users reported reduced fatigue and 33.3% improved mood. There were significant correlations between CAM use and lower social and professional status (p < 0.04), disease progression (p < 0.03), and lack of efficacy of disease-modifying therapies (p < 0.04). There were no significant correlations between CAM usage and sex, habitation, education, marital or professional status. The most frequently used CAMs were vitamins (48%), and polyunsaturated fatty acids (36%); psychophysical methods (44%) included manual therapies (24%) and relaxation techniques (17.3%) as well as herbal medicine (29.3%). Physicians were considered to be the most reliable authority in both conventional treatment (97.3%) and CAM (67%). Complementary and alternative medicine users significantly more often discussed this issue with their doctors (56%) compared to patients who did not use alternative medicine (p < 0.05). However, 54% of patients did not inform their physician about CAM use. Responders said that physicians did not initiate discussion about it (55.9%), but 44% of patients would like to have the possibility of talking to a doctor about CAM. CONCLUSIONS AND CLINICAL IMPLICATIONS: Although CAM efficacy and safety is not confirmed, one should keep in mind that most MS patients use alternative methods, especially those individuals with a more severe phenotype. Physicians are mostly perceived as reliable authorities and therefore they should discuss this issue with patients in order to eliminate drug interactions and to improve compliance.

Pseudobulbar affect in neurodegenerative diseases: A systematic review and meta-analysis.

BACKGROUND: Pseudobulbar affect (PBA) is characterized by uncontrolled episodes of crying and laughing which is associated with a variety of neurological diseases including traumatic brain injury, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), brain tumors, stroke, Parkinson's disease (PD), Alzheimer's disease (AD) and other dementias. However, there is a lack of exact estimated prevalence of PBA among neurological disorders. AIM: In this systematic review and meta-analysis study we aimed to assess the prevalence of PBA in four neurodegenerative diseases including ALS, MS, AD, and PD. METHODS: PubMed, Scopus, and Web of Science were searched in July 2021 for studies that reported the prevalence of PBA in ALS, MS, AD, and PD patients. The mean point of PBA prevalence and odds ratios were calculated as effect size (ES) using the random-effect model with a 95% confidence interval (CI). RESULTS: The summarized prevalence of PBA was of PBA in PD patients were ranged between 1% and 31% with an overall meta-analysis prevalence of 16.5% and high heterogeneity (I2: 98.7%, p: 0.000). Patients with ALS showed a PBA prevalence of 38.5%, which is higher than other neurodegenerative diseases (CI 95%: 31%-45%, I2: 61.4%, p: 0.034). Moreover, the prevalence of PBA in MS patients in the analysis was 23.3% ranging between 11% and 35% with high-level heterogeneity according to the I2 value (I2: 98.9%, p: 0.000). Also, our meta-analysis showed that the PBA prevalence in AD was 16.4% (CI 95%: 7%-25%) with high heterogeneity (I2: 97.8%, p: 0.000). CONCLUSION: This review showed that PBA is common in patients with neurodegenerative diseases including PD, AD, MS, and especially ALS. Due to the lack of proper recognition, medication and treatment would not be effective and sufficient. Therefore, it can dramatically lower the quality of life in PBA patients and decrease their social interactions.

The impact of lifetime coffee and tea loads on Multiple Sclerosis severity.

BACKGROUND AND AIMS: The association between lifestyle factors and Multiple Sclerosis (MS) disease severity and progression has been investigated to a lesser extent compared with susceptibility to the disease. We aimed to assess the impact of lifetime coffee and tea consumption on MS severity. METHODS: Design: cross-sectional study. Two hundred and eight patients (139 females and 69 males) consecutively recruited at the Department of Neurology in Novara, Italy were asked about their lifetime consumption of coffee and tea. The lifetime intensity of consumption (cups/day) was estimated as the weighted sum of the mean number of standard cups drunk per day at different ages. A measure of cumulative lifetime load of the exposure was expressed in terms of cup-years. Disease severity was estimated by the Multiple Sclerosis Severity Score (MSSS). HLA-DRB1∗15 and HLA-A∗02 genotyping was performed in 167 patients. RESULTS: The MSSS was not associated with the status of coffee or tea consumer, or the amount of cups/day or cup-years. The Odds Ratios (OR) for falling in the upper tertile of the MSSS distribution was 1.30 (95% Confidence Interval (CI): 0.47-3.58) for coffee consumers of 1-3 cups/day and 1.14 (95%CI: 0.33-3.95) for 4-8 cups/day vs. non-consumers. The OR was 0.69 (95%CI: 0.35-1.34) for tea consumers vs. non-consumers. However, heavy consumers of coffee (4-8 cups/day) more frequently had a progressive form than small consumers (1-3 cups/day) and non-consumers (19% vs. 14% vs. 0%), and had a significantly higher age at MS onset (36.6 ± 10.3; 31.5 ± 9.5; 28.6 ± 8.1 years, p = 0.001). Although not reaching statistical significance, coffee consumers positive for HLA-A∗02 had a six-fold risk of being in the worst tertile compared to never consumers, whereas the risk was only 1.3 for coffee consumers negative for the same allele. CONCLUSIONS: Coffee or tea intake is not associated with different severity of MS. However, we cannot exclude a possible effect of higher doses of coffee for the subgroup of progressive patients.

Waterpipe Tobacco Smoking and Other Multiple Sclerosis Environmental Risk Factors.

INTRODUCTION: There are a number of well-established risk factors for multiple sclerosis (MS). Other factors, however, showed conflicting or inconsistent results. Here, we examine some factors that are unique to or more practiced in Saudi Arabia (SA) and the Arab region such as waterpipe tobacco smoking (WTS), face veiling, raw milk (RM) and camel milk (CM) consumption, and tuberculosis (TB) infection in addition to other traditional factors. METHODS: This is a sex- and age-matched case-control study in which we used a structured questionnaire to examine the relation between a number of factors and exposures and the risk of MS. Three hundred MS patients and 601 controls were included. Data were analyzed across different statistical models using logistic regression adjusting for age, sex, marital status, duration of breastfeeding, age first joining school, coffee consumption, and face exposure. RESULTS: Cigarette smoking (OR = 1.79, [95% CI: 1.01-3.17], p = 0.047), WTS (OR = 2.25, [95% CI: 1.21-4.15], p = 0.010), and CM consumption (OR = 2.50, [95% CI: 1.20-5.21], p = 0.014) increased the risk of MS, while performing hajj (OR = 0.47, [95% CI: 0.34-0.67], p = 0.001), TB infection (OR = 0.29, [95% CI: 0.11-0.78], p = 0.015), face veiling (OR = 0.32, [95% CI: 0.23-0.47], p = 0.001), and coffee consumption (OR = 0.67, [95% CI: 0.49-0.89], p = 0.008) appeared to be associated with decreased risk. No association was found between fast food, processed meat, soft drinks, animal milk (other than camel), or RM consumption and the risk of MS. CONCLUSION: The results of this case-control study confirm that different means of tobacco smoking are associated with increased risk of MS. It also sheds more light on the complex association between infections and MS.

Clinical perspective on pain in multiple sclerosis.

Pain is an important and frequent symptom in multiple sclerosis (MS), which leads to a low quality of life, increased disability level, and lack of employment and mental health. Recently, studies have shown increased interest in pain in MS and there is a growing evidence of its prevalence. However, the literature suffers from lack of experimental studies focusing on pain reduction. This topical review summarizes the current knowledge about pain in MS with its definitions, assessments, treatments and rehabilitation within a holistic perspective.

[The Multiple Sclerosis Health Resource Utilization Survey]. / Der Multiple Sclerosis Health Resource Utilization Survey.

BACKGROUND: In health economic studies, valid and reliable cost data are essential to reach meaningful conclusions. In the case of multiple sclerosis (MS), such studies are often based on primary data for which the underlying survey instruments have not been published. In addition, heterogeneous methods make the comparability and interpretation of such study results difficult. To standardize health economic studies in MS, the Multiple Sclerosis Health Resource Utilization Survey (MS-HRS) was developed, validated and published in a freely accessible format. RESEARCH QUESTION: This review focuses on the MS-HRS. We report on the methodological background of studies on the assessment of cost of illness as well as MS-HRS-based results on the costs of disease dynamics in people with MS. METHODS: This article is based on a selective literature review on the MS-HRS as well as on health economic aspects of cost assessment. RESULTS: The MS-HRS provides a holistic assessment of direct medical, direct non-medical and indirect resource utilization. Within indirect costs, we considered absenteeism, either short term (sick leave) or long term (disability pension), but also presenteeism, which refers to impaired performance during work. Resources were valued at the societal opportunity cost or the best possible approximation. First analyses based on MS-HRS showed that, in addition to inpatient disease severity and clinical course, disease dynamics in form of relapses and progression have enormous socioeconomic implications. CONCLUSION: Valid cost data bring transparency to the economic consequences of diseases. In addition to clinical data, cost data can be used to determine cost-effectiveness and thus reveal opportunities for more efficient patient care. For the case of MS, a freely accessible tool is available for cost assessments.

Association between multiple sclerosis and dietary patterns based on the traditional concept of food nature: a case-control study in Iran.

INTRODUCTION: It remains a matter of debate whether traditional concepts regarding the nature of food affect the development and progression of multiple sclerosis (MS).To date, there are limited studies that have investigated the association between MS and dietary patterns based on the categories of food nature (hot, cold, or balanced) defined in traditional medicine. METHOD: This case-control study was conducted from October 2019 to February 2020. In total, 60 patients diagnosed with MS within the preceding 6 months and referred to our neurology outpatient clinic were included in our case group. The control group included 180 patients who were referred to the same center for general or orthopedic surgery. Dietary intake was assessed in both groups through a reliable and valid semi-quantitative food frequency questionnaire. Data were assessed using principal component analysis. RESULTS: The mean age of the participants was 44.9 ± 17.33 years. The analysis showed that four food patterns were distinguished (eigenvalue > 1), namely "additives and cold-natured foods", "hot and balanced foods and nuts", "dairy and legumes", and "hot and balanced starches". These food patterns explained 57.8% of the total variance. After adjusting all confounding factors, individuals in the highest quartile and medium quartile of "additives and cold-natured foods" had an elevated MS risk compared with the lowest quartile (OR = 7.21, 95%CI = 2.01-12.38 and OR = 3.37, 95%CI = 1.02-11.35, respectively). Furthermore, individuals in the highest quartile of the "hot and balanced foods and nuts" group were protected against MS compared with its lowest quartile (OR = 0.28, 95%CI = 0.08-0.90). Moreover, a protective effect against MS was seen in the highest quartile of the "hot and balanced starches" group relative to its lowest quartile (OR = 0.34, 95%CI = 0.12-0.98). No significant association was found between "dairy and legumes" and the risk of MS. CONCLUSION: This study revealed that dietary patterns based on the traditional concept of food nature might be associated with the risk of developing MS. This represents the first work in this area, so further research is recommended.

Dietary risk factors of primary progressive multiple sclerosis: A population-based case-control study.

OBJECTIVES: There are growing evidences on the role of nutritional factors in multiple sclerosis (MS) occurrence. But dietary data are limited in primary progressive type of MS (PPMS). We assessed the role of dietary factors during adolescence in PPMS risk. METHODS: An incident case-control study on 143 PPMS cases with definite diagnosis and 400 controls were conducted in Sina hospital, Tehran, Iran. Demographic data were collected. Data on nutritional habits during adolescence were obtained using questionnaire designed for multinational case-control studies of environmental risk factors for multiple sclerosis (EnvIMS-Q). Logistic regression models were run to evaluate the role of diet in PPMS risk. RESULTS: A significant association was founded between higher intake of dairy, seafood, red meat, poultry, vegetable, fruit and nut and lower risk of PPMS (P< 00.5). This association was dose dependent for all mentioned food groups except fruit. In the fully adjusted model, more intake of dairy (OR: 0.27; 95%CI: 0.14-0.53), seafood (OR: 0.21; 95%CI: 0.10-0.44), red meat (OR:0.44; 95%CI: 0.22-0.90), vegetable (OR: 0.19; 95%CI: 0.09-0.39), fruit (OR: 0.47; 95%CI: 0.22-0.99) and nut (OR: 0.29; 95%CI: 0.15-0.56) in the third tertiles resulted in significant reduction in PPMS risk. In case of poultry consumption, the association was meaningful just in the third tertile of crude model (OR: 0.54; 95%CI: 0.30-0.95). Nutrient supplementation with calcium, iron, folic acid, vitamin B12 and C were also related with more than 84% lower risk of PPMS. CONCLUSION: Our data proposed that adequate intake of food groups and nutrient supplementation during adolescence may be effective in reducing adult-onset PPMS risk.

Multiple sclerosis incidence rate in southern Iran: a Bayesian epidemiological study.

BACKGROUND: Multiple Sclerosis (MS) remains to be a public health challenge, due to its unknown biological mechanisms and clinical impacts on young people. The prevalence of this disease in Iran is reported to be 5.30 to 74.28 per 100,000-person. Because of high prevalence of this disease in Fars province, the purpose of this study was to assess the spatial pattern of MS incidence rate by modeling both the associations s of spatial dependence between neighboring regions and risk factors in a Bayesian Poisson model, which can lead to the improvement of health resource allocation decisions. METHOD: Data from 5468 patients diagnosed with MS were collected, according to the McDonald's criteria. New cases of MS were reported by the MS Society of Fars province from 1991 until 2016. The association between the percentage of people with low vitamin D intake, smoking, abnormal BMI and alcohol consumption in addition to spatial structure in a Bayesian spatio-temporal hierarchical model were used to determine the relative risk and trend of MS incidence rate in 29 counties of Fars province. RESULTS: County-level crude incidence rates ranged from 0.22 to 11.31 cases per 100,000-person population. The highest relative risk was estimated at 1.80 in the county of Shiraz, the capital of Fars province, while the lowest relative risk was estimated at 0.11 in Zarindasht county in southern of Fars. The percentages of vitamin D supplementation intake and smoking were significantly associated with the incidence rate of MS. The results showed that 1% increase in vitamin D supplementation intake is associated with 2% decrease in the risk of MS and 1% increase in smoking is associated with 16% increase in the risk of MS. CONCLUSION: Bayesian spatio-temporal analysis of MS incidence rate revealed that the trend in the south and south east of Fars province is less steep than the mean trend of this disease. The lower incidence rate was associated with a higher percentage of vitamin D supplementation intake and a lower percentage of smoking. Previous studies have also shown that smoking and low vitamin D, among all covariates or risk factors, might be associated with high incidence of MS.

Prevalence of pediatric multiple sclerosis in Germany: A nationwide population-based analysis.

BACKGROUND AND PURPOSE: Prevalence data are needed to reveal trends regarding the pediatric multiple sclerosis (MS) situation worldwide. The aim was to identify changes in MS diagnosis prevalence in pediatric patients over a 10-year period in Germany. METHODS: This analysis is based on nationwide outpatient claims data of children aged <18 years covered by the German statutory health insurance (n = 11,381,939 in 2018). People with MS (PwMS) had ≥1 documented MS diagnosis (International Classification of Diseases, 10th Revision, German modification code G35.x). The annual pediatric MS diagnosis prevalence was analyzed regarding age, sex, and place of residence during 2009-2018. RESULTS: The prevalence of pediatric MS developed from 5.3 (2009) to 5.4 (2018)/100,000 insured population aged <18 years. The MS prevalence in patients aged 15-17 years showed a moderate increase over 10 years (19.6-22.7/100,000), whereas patients ≤14 years old showed a slight decrease (1.9-1.7/100,000). The sex ratio (female:male) in 2018 was relatively balanced in PwMS aged ≤14 years (1.32) but female-dominated in those aged 15-17 years (2.47). The formerly different prevalence of pediatric MS between East and West Germany has converged since 2012. CONCLUSIONS: So far, this is the largest study of pediatric MS prevalence in terms of source population size (87% of German children <18 years of age, n = 11,381,939 in 2018) and study period (2009-2018) worldwide. The analyses revealed an increase in MS prevalence and a female-dominated sex ratio in "older" adolescents compared to younger patients.

A cross-sectional survey of cannabis use by people with MS in Oregon and Southwest Washington.

BACKGROUND: Evidence supports that cannabinoids reduce self-reported spasticity and neuropathic pain in people with MS (PwMS), and legal access to cannabis for medical and recreational use continues to rise. However, there are limited data regarding patterns of cannabis use and perceived benefits of cannabis among PwMS in the US. This study describes the prevalence of cannabis use, routes of administration, perceived benefit of cannabis for MS, and characteristics associated with cannabis use and perception of benefit among a population of PwMS living in two states where cannabis is legal for both medical and recreational use. METHODS: A survey about treatments used by PwMS, focusing on complementary and alternative medicine (CAM), was sent to PwMS living in Oregon and Southwest Washington. This survey included questions about current and past cannabis use, route of cannabis administration, and perceived benefits, as well as personal demographics. RESULTS: Of the 1188 returned surveys, 1000 had at least 75% complete survey responses and also completed the questions about current and past cannabis use. Thirty percent (n=303) of respondents reported currently using cannabis, 21% (n=210) used in the past but not currently, and 49% (n=487) had never used cannabis. Among current users, rates of use by smoking, vaping, topicals, tinctures and oils, or edibles were similar (35-46%), and most (59%) reported using multiple routes of administration. Most (64-78%, varying by route) current and past users reported cannabis being very or somewhat beneficial for their MS. The odds of current cannabis use were higher in PwMS who: 1) were younger (OR 2.24 [95% CI 1.39-3.61] for those age 18-40 compared with age >60]; 2) had lower household income (OR 3.94 [95% CI 2.55-6.09] with annual income <$25k compared with those with >$100k); 3) had secondary progressive MS (OR 1.77 [95% CI 1.07-2.92]); and 4) had more than minimal MS disability (OR 2.05 [95% CI 1.03-4.10] for those using a walker compared to those with none/minimal disability). The odds of perceiving cannabis as beneficial for MS were higher in: 1) younger individuals (OR 5.61 [95% CI 2.62-11.98] for those age 18-40 compared with age >60); 2) those with lower household income (OR 3.35 [95% CI 1.65-6.80] with annual income <$25k compared with those with >$100k), 3) those not currently using disease modifying therapies (OR 2.32 [95% CI 1.30-4.13]), and 4) those with the greatest disability (OR 17.96; [95% CI 2.00-161.22]). CONCLUSION: In this survey, 30% of PwMS reported currently using cannabis for their MS, mostly by multiple routes of administration, and most of these people report this being helpful for their MS. People who were younger, had lower household income, had progressive disease, and had more than minimal disability were more likely to use cannabis and report it was beneficial for their MS. People who were not using disease modifying therapies were also more likely to report benefit from cannabis use.

Reduction in circulating vitamin D binding protein in patients with multiple sclerosis.

BACKGROUND: In this study, we aimed to determine the risk association between vitamin D binding protein (VDBP) polymorphism in patients with multiple sclerosis (MS) in a MS biobank and the difference in VDBP serum levels in MS patients who were recently diagnosed. METHOD: The current case-control study was performed on 296 MS patients and 313 controls. Thereafter, two common missense VDBP polymorphisms, named rs7041and rs4588, were evaluated in all the participants. Serum levels of vitamin D and vitamin D binding protein were assessed in 77 MS patients who were diagnosed since one year ago and in 67 healthy people who were matched in terms of age and sex. RESULT: The frequency distributions of VDBP genotypes and alleles of SNP rs7041 and rs4588 were observed to be similar in both the MS and control groups (p > 0.05). The VDBP haplotypes, as Gc2/Gc2, Gc1/Gc1, and Gc1/Gc2, were found to be similar in the MS and control groups (p > 0.05). In subgroup analysis, circulating VDBP was lower in MS patients (Ln-VDBP (µgr/ml): 3.64 ± 0.91 vs. 5.31 ± 0.77, p = 0.0001) even after adjusting for vitamin D levels, body mass index, and taking vitamin D supplement. There was no significant association between VDBP haplotypes and vitamin D levels in the two groups. CONCLUSION: The present study suggested an association between lower levels of circulating VDBP and multiple sclerosis in newly diagnosed patients. However, the VDBP causative role in the development of MS is still unclear, so it needs more studies.

Methylxanthines and Neurodegenerative Diseases: An Update.

Methylxanthines (MTX) are purine derived xanthine derivatives. Whereas naturally occurring methylxanthines like caffeine, theophylline or theobromine are widely consumed in food, several synthetic but also non-synthetic methylxanthines are used as pharmaceuticals, in particular in treating airway constrictions. Besides the well-established bronchoprotective effects, methylxanthines are also known to have anti-inflammatory and anti-oxidative properties, mediate changes in lipid homeostasis and have neuroprotective effects. Known molecular mechanisms include adenosine receptor antagonism, phosphodiesterase inhibition, effects on the cholinergic system, wnt signaling, histone deacetylase activation and gene regulation. By affecting several pathways associated with neurodegenerative diseases via different pleiotropic mechanisms and due to its moderate side effects, intake of methylxanthines have been suggested to be an interesting approach in dealing with neurodegeneration. Especially in the past years, the impact of methylxanthines in neurodegenerative diseases has been extensively studied and several new aspects have been elucidated. In this review we summarize the findings of methylxanthines linked to Alzheimer´s disease, Parkinson's disease and Multiple Sclerosis since 2017, focusing on epidemiological and clinical studies and addressing the underlying molecular mechanisms in cell culture experiments and animal studies in order to assess the neuroprotective potential of methylxanthines in these diseases.