The prevalence of multiple sclerosis in the District of Santarém, Portugal

The prevalence of multiple sclerosis (MS) in Portugal is still unknown. Recent studies conducted in southern European countries showed higher than expected rates of MS prevalence.In an attempt to evaluate the MS prevalence in Santarém--a district with 62621 inhabitants (1991 census) located in the centre of Portugal--we have conducted a population survey in this district for five years. The crude prevalence rate found was 46.3/100,000. This figure is not different from findings recently reported in studies conducted at similar latitudes in neighbour southern European countries. This was the first population survey conducted in Portugal, and it is the first accurate contribution to the knowledge of the MS prevalence in this country.     

The prevalence of multiple sclerosis in the city of São Paulo, Brazil, 1997

July 1, 1997 was stipulated as the day for estimating the prevalence of multiple sclerosis within the city of São Paulo. The patients were identified via various sources, including associated universities and magnetic resonance services of the city of São Paulo. The area covered by the study has a population of 9,380,000, mainly white and of European origin, with a large number of immigrants from Spain and Portugal. The patients were classified in accordance with the criteria of Poser et al. (1983), and only those with defined multiple sclerosis were registered. The study gave a prevalence of 15.0/10⁵ inhabitants, or three times the value obtained in a similar study in 1990. This increase reveals the larger number of cases encompassed by the study, and is attributed to the use of more detailed recording methods, improvements in diagnosis, and better conditions for treatment.     

Identification of the miRNA–mRNA regulatory network in multiple sclerosis

Objectives: Multiple sclerosis (MS) is the common neurological disorders in young adults, which affects the central nervous system myelin or oligodendrocytes and results in disability. This study aimed to identify the key miRNAs in blood of patients in MS for better understanding the underlying mechanisms of MS.

Methods: The publicly available Gene Expression Omnibus data-sets of MS were performed to integrated analysis. miRNA expression and mRNA expression were analyzed in whole blood samples from patients with MS and healthy controls by microarray analysis, Gene Ontology enrichment analyses, Kyoto Encyclopedia of Genes and Genomes pathway analyses, construction of miRNA–mRNA interaction network, and quantitative real-time polymerase reaction.

Results: In patients with MS, microarray analysis identified 45 significantly dysregulated miRNAs and 621 significantly dysregulated mRNAs. 1165 negative correlation pairs of miRNA–mRNA were predicted and used to construct the interaction network. hsa-miR-30a, hsa-miR-93, hsa-miR-20b, and hsa-miR-20a occurred as central hubs regulating 87, 38, 34, and 34 genes. Dysregulated mRNAs were significantly enriched in ribosome, tuberculosis, and pathways in cancer. The verification of qRT-PCR displayed that hsa-miR-328-3p was significantly up-regulated in MS and its target genes RAC2 had the down-regulated tendency in MS. hsa-miR-20a-5p had the up-regulated tendency and the corresponding target gene EIF4EBP2 had the down-regulated tendency in MS compared to healthy controls.

Discussion: hsa-miR-30a, hsa-miR-93, hsa-miR-20b, and hsa-miR-20a might be the key participant in the pathophysiology of MS involved in signaling pathways including ribosome, tuberculosis, and pathways in cancer.     

The direct costs of multiple sclerosis—study in the Czech Republic

Background

Multiple sclerosis (MS) is a progressive autoimmune disease of the central nervous system that is often disabling and for which there is currently no cure, though disease-modifying treatment is now available. The aim of this study is to describe the current values of the direct costs of multiple sclerosis (MS) in the Czech Republic.

Methods

Attention is focused on direct medical costs. The costs were monitored in the Czech Republic among 5673 patients in the period between 2011 and 2015. These costs included complex, special and targeted visits at the neurologist, blood collection and the costs of hospitalisation. The results refer to the diagnoses according to the International Statistical Classification of Diseases and Related Health Problems. The attention is focused on MS G35 (NS; brain stem; spinal cord; disseminated; generalised).

Results

The average total direct costs per patient per year are 4838.1 €. Not every patient has to be hospitalised during the year, and not every patient has prescribed medication. According to the above data, 12% of patients are hospitalised and 55% of patients are prescribed medication. The minimum average cost per patient without medication and hospitalisation is 54.1 €.

Conclusion

Cost evaluation across countries is difficult due to the different evidence. If only selected direct costs considered in this study are compared, the absolute economics burden increases over time. The only statistically significant difference in the average price and the time spent is between 2012 and 2013, where the correlation value is 0.597.

     

Cognitive assessment in multiple sclerosis—an Italian consensus

The aim of this consensus paper was to define the state of the art on cognitive assessment of persons with multiple sclerosis (PwMS), with the purpose of providing recommendations for the Italian centers involved in MS management. While there are no formal guidelines published regarding the assessment of cognitive function in MS, on the basis of an expert opinion meeting, held in Milan (Italy) on July 4, 2016, we report the recommendations of a panel of Italian experts including MS neurologists and neuropsychologists for the assessment and follow-up of cognitive function in adult MS subjects.     

The prevalence of multiple sclerosis in Tayside, Scotland: do latitudinal gradients really exist?

To determine the prevalence of multiple sclerosis (MS) in the Tayside Health Board Area, Scotland, we carried out a population-based survey using four intersecting sources (Neurology Department records, a survey of general practitioners, Scottish Morbidity Records of discharges from hospitals and visual evoked response requests). A two-source capture-recapture model estimated survey coverage, and direct age-sex standardisation was used to take account of different population structures. Comparisons were made between the prevalence in Scotland and that in the rest of the United Kingdom. A total of 727 (definite and probable) and 880 cases (early, probable and possible) were identified using the criteria of Poser et al. and those of Allison and Millar in a population of 395,600 (1995 mid-year estimate). The prevalence of MS on 1 September 1996 was 184/100,000 (95% confidence interval 171–198) and 222/100,000 (95% confidence interval 210–240), respectively. The two-source capture-recapture model estimated that the survey was between 93% and 99% complete. Age-sex standardisation eliminated certain north-south differences in prevalence when comparisons were made with previous surveys. Diagnostic misclassification may also have influenced reported prevalence statistics. The prevalence is similar to that found in revised figures from the Grampian region in Scotland but significantly higher than recent estimates from England and Wales. Methodological differences may account for most of the reported differences between north and south, although there is still evidence to suggest that MS is more prevalent in northern Great Britain and Northern Ireland than in England and Wales. Received: 12 October 1998 Received in revised form: 27 May 1999 Accepted: 8 June 1999     

Trends in prevalence and incidence of multiple sclerosis in Bajo Aragón, Spain

OBJECTIVE: Recent reports provide consistent evidence that Spain is an area of high risk for multiple sclerosis (MS) according to prevalence surveys. However, the studies of incidence are scarce. The objective of the current work is to analyse whether the increased prevalence of MS is accompanied by increasing incidence in the area of Bajo Aragón, northeastern Spain. METHODS: The data of both prevalence and incidence were retrieved from a prospective register created in 1994 and which included patients with probable or definite MS. Crude and age-standardised rates were calculated from 1994 to 2002 and compared with those found retrospectively in the previous period of 1984-1993. RESULTS: In January 2003, we found a prevalence rate of 75/100,000 (95% CI: 52-97) whereas it was 35/100,000 (95% CI: 20-50) in 1994. In a period of 9 years, 25 new cases were diagnosed in the area with a mean annual incidence rate of 4.6/100,000 (95% CI: 2.8-6.5; range: 1.6-13.6) in comparison to 17 new cases from 1984 to 1993 with a mean incidence rate of 3/100,000 (95% CI: 1.6-4.5). The standardised ratio of incidences was 1.44 (95% CI: 0.95-2.17) and, therefore, the difference of rates was not significant. CONCLUSION: We conclude that the increase in prevalence of MS is more likely to be due to improvement on case ascertainment than to increasing incidence. Nonetheless, further prospective incidence studies in larger populations are warranted in Spain to elucidate whether the frequency of this disease is truly increasing.     

The prevalence of multiple sclerosis, distribution of clinical forms of the disease and functional status of patients in Csongrád County, Hungary.

OBJECTIVE: The aim of this study was to determine the prevalence of multiple sclerosis (MS) in the population of Csongrád County, Hungary (400,128 inhabitants) and to determine the functional status (based on the Expanded Disability Status Scale; EDSS) of the patients according to the clinical forms of the disease. METHODS: The diagnosis was established with the aid of the Poser diagnostic criteria, and the degree of physical disability was determined using the Kurtzke EDSS. RESULTS: In Csongrád County, the prevalence of MS is 62/100,000. The distribution of patients according to the clinical forms of MS was as follows: 15% had the benign form, 54% had relapsing-remitting MS, 20% had secondary chronic progressive MS and 11% had the primary chronic progressive form of MS. Sixty percent of relapsing-remitting MS patients had an EDSS score of 0-4 points and 33% had an EDSS score of 4.5-6.5 points. CONCLUSION: The distribution of patients according to the clinical forms of the disease in this representative population is comparable to results in other regions of the world.     

Interferon beta in relapsing–remitting multiple sclerosis

Background and objective Long–term observational studies may provide additional information about the behaviour of different drugs in the post–marketing period. We present the data of our cohort of relapsing–remitting multiple sclerosis (RRMS) patients treated with interferon beta (IFNβ). Methods We analysed RRMS patients followed for at least 2 years. From 1995, we initiated therapy with IFNβ.As they became available, patients were allocated to one of the IFNs at standard doses (IFNβ–1b, IFNβ–1a i. m. or IFNβ–1a s. c.). Each patient was included in a follow–up protocol containing demographic and baseline clinical data. Results Between 1995 and 2004, 382 patients have completed at least 2 years of follow–up. Significant differences at entry were observed. Patients on IFNβ–1b had a higher disease activity and disability at baseline than those on IFNβ–1a i. m. or IFNβ–1a s. c. A significant reduction in the relapse rate was observed for the three drugs (70 % for IFNβ–1b, 64% for IFNβ–1a i. m. and 74 % for IFNβ–1a s. c.). We observed a sustained progression of disability in 11% of patients on IFNβ–1b, 17% on IFNβ–1a i. m. and 19% on IFNβ–1a s. c.; and at four years of follow–up in 24% of patients on IFNβ–1b, 23% on IFNβ–1a i. m. and 35% on IFNβ–1a s. c. No unexpected major adverse events were observed with any of the drugs. Conclusions Interferon beta is safe and well tolerated. The various registered interferon beta drugs provide a comparable efficacy in a large non–selected cohort of RRMS patients.     

Are astrocytes central players in the pathophysiology of multiple sclerosis?

An interaction between antimyelin T cells and antigen-presenting glial cells is a crucial step in the cascade of immune events that lead to the inflammatory lesions in multiple sclerosis (MS). One of the most debated and controversial issues is whether microglial cells or astrocytes are the key players in initiating the (auto)immune reactions in the central nervous system in MS. Many investigators consider microglia to be the responsible intrinsic immunoeffector cells. In this review, we speculate that in MS astrocytes may serve as primary (facultative) antigen-presenting cells due to a failure of noradrenergic suppression of class II major histocompatibility complex molecules, which is caused by a loss of beta(2)-adrenergic receptors. If this hypothesis is correct, pharmacologic suppression of the antigen-presenting capacities of astrocytes may be a potential therapy for MS.     

The role of osteopontin: A shared pathway in the pathogenesis of multiple sclerosis and osteoporosis?

Osteopontin (OPN) was suggested to have a role in the pathophysiology of MS and in bone metabolism. However, we formerly reported increased presence of osteoporosis in MS patients independent of corticosteroid treatment, there is only limited information about the mechanism of bone loss. In this study, we investigated the role of OPN on bone mineral density in MS patients. Thirty-three relapsing-remitting (RR), 12 secondary progressive (SP), and 5 primary progressive (PP) MS patients and 30 healthy controls were prospectively enrolled. Students' t test, chi-square test, and Pearson correlations were used. The mean OPN level was 155.4+/-81.8 ng/ml in controls, and 15.9+/-36.2 ng/ml in MS patients (p<0.001).No statistical difference was observed among RR, SP and PPMS patients (p=0.162). No relationship was found between OPN levels and age at onset of disease (p=0.830), gender (p=0.785), MS subtypes (p=0.330), disease duration (p=0.744), or EDSS scores (p=0.633).About 34% of MS patients versus 10.3% of controls had osteoporosis (p=0.017).Osteopontin levels showed no significant correlation with osteoporosis in controls, but were lower in MS patients with osteoporosis in femur neck (r=0.85, p=0.010).The cumulative dose of corticosteroid treatment did not correlate with OPN levels (p=0.285).In conclusion, our results suggest that OPN may have a role as a shared cytokine in pathogenesis of MS and osteoporosis.     

Metabolite changes in early relapsing–remitting multiple sclerosis

Previous in vivo proton magnetic resonance spectroscopic imaging (¹H–MRSI) studies have found reduced levels of N–acetyl–aspartate (NAA) in multiple sclerosis (MS) lesions, the surrounding normal–appearing white matter (NAWM) and cortical grey matter (CGM), suggesting neuronal and axonal dysfunction and loss. Other metabolites, such as myoinositol (Ins), creatine (Cr), choline (Cho), and glutamate plus glutamine (Glx), can also be quantified by ¹H–MRSI, and studies have indicated that concentrations of these metabolites may also be altered in MS. Relatively little is known about the time course of such metabolite changes. This preliminary study aimed to characterise changes in total NAA (tNAA, the sum of NAA and N–acetyl–aspartyl–glutamate), Cr, Cho, Ins and Glx concentrations in NAWM and in CGM, and their relationship with clinical outcome, in subjects with clinically early relapsing–remitting MS (RRMS). Twenty RRMS subjects and 10 healthy control subjects underwent ¹H–MRSI examinations yearly for two years. Using the LCModel, tNAA, Cr, Cho, Ins and Glx concentrations were estimated both in NAWM and CGM.At baseline, the concentration of tNAA was significantly reduced in the NAWM of the MS patients compared to the control group (–7%, p = 0.003), as well as in the CGM (–8.7%, p = 0.009). NAWM tNAA concentrations tended to recover from baseline, but otherwise tissue metabolite profiles did not significantly change in the MS subjects, or relatively between MS and healthy control subjects. While neuronal and axonal damage is apparent from the early clinical stages of MS, this study suggests that initially it may be partly reversible. Compared with other MR imaging measures, serial ¹H–MRSI may be relatively less sensitive to progressive pathological tissue changes in early RRMS.