Greek Multiple Sclerosis Patients Research Articles

A Prospective, Observational, Cohort Study to Assess the Efficacy and Safety of Prolonged-Release Fampridine in Cognition, Fatigue, Depression, and Quality of Life in Multiple Sclerosis Patients: The FAMILY Study.

IntroductionThe efficacy of prolonged-release fampridine (PR-FAM) may extend in multiple sclerosis (MS) beyond walking ability. The objective of this study was to evaluate the effect of PR-FAM treatment on cognition, fatigue, depression, and quality of life (QoL) in adult patients with MS in a real-world setting.MethodsFAMILY was a multi-center, prospective, observational, real-world cohort study of MS patients receiving PR-FAM in the outpatient setting. Patients were treated as per PR-FAM’s local prescribing information for 6 months. Standardized protocols and questionnaires were used to evaluate changes in cognition (PASAT; Paced Auditory Serial Addition Test), fatigue (MFIS; Modified Fatigue Impact Scale), depression (BDI-II; Beck Depression Inventory-II) and QoL (MusiQoL; MS International Quality-of-Life questionnaire, MSIS-29; Multiple Sclerosis Impact Scale: PHYS and PSYCH subscales) at 3 and 6 months compared to baseline.ResultsIn total, 102 eligible patients from 8 sites in Greece were analysed, of whom 92 completed the study and 10 discontinued. At 6 months, PR-FAM treatment resulted in improvements from baseline in PASAT-3′′ (p = 0.044), MFIS (p < 0.001), BDI-II (p < 0.001), MusiQoL (p < 0.001) and MSIS-29-PHYS (p = 0.012) and MSIS-PSYCH (p < 0.001). A positive effect was evident already at 3 months in PASAT-3′′ (ns), MFIS (p = 0.020), BDI-II (p = 0.034), MusiQoL (p = 0.001), MSIS-29-PHYS (ns) and MSIS-29-PSYCH (p < 0.001).ConclusionsThis observational study provides new data to the current literature in support of PR-FAM’s positive effects in cognition, fatigue, depression, and QoL in a large, heterogeneous group of Greek MS patients in the real-world setting.Trial RegistrationClinicalTrials.gov identifier, NCT03164018.Supplementary MaterialThe online version of this article (10.1007/s12325-020-01606-5) contains supplementary material, which is available to authorized users.

The Multiple Sclerosis Intimacy and Sexuality Questionnaire (MSISQ-15): Validation and Cross-cultural Adaptation of the Greek Version in MS Patients

Sexuality and intimate relationships are a significant part of life and well-being. The presence of a physical illness such as multiple sclerosis (MS) has the potential to complicate the lifelong course of sexual development and the ways in which one defines and expresses one’s sexuality. The objective of this study was to develop a cross-cultural adaptation and validation of the MSISQ-15 so that it can be used as a tool to evaluate SD in Greek patients with MS. A total of 127 individuals, 68 Greek MS patients and 59 healthy persons for the control group who visited urology department of the National Rehabilitation Centre of Athens completed the Greek version of MSISQ-15 along with Female Sexual Function Index for women and International Index of Erection Function at baseline (test) and 3 weeks later for the MS patients, (retest). Data were analyzed for measurement properties. Content validity was adequate. The Greek version of MSISQ-15 showed a good internal consistency with Cronbach’s a > 70 for total score and the three scales of MSISQ-15 for the test and retest. In the MS patient group, no floor or ceiling effects were seen for the total score, primary, secondary and tertiary symptoms. A test–retest reliability shows that for primary symptoms and measurements 3 weeks after, correlation was r = .94, for secondary was r = .88, while for tertiary was r = .89. All correlations were significant at p < .001. In conclusion, this Greek version of MSISQ-15 was tested following well-established guidelines on measurement properties and showed good validity and reliability. It is reproducible, reliable and valid for the Greek population and may be used as a tool for assessing the impact of sexual dysfunction in patients with MS.

Prevalence of Sexual Dysfunction Among Greek MS Patients

Multiple Sclerosis (MS) can complicate the lifelong course of sexual development and the ways in which one defines and expresses one’s sexuality. The aim of the present study was to register, examine and categorize sexual dysfunction (SD) among Greek patients with MS. 866 individuals, all Greek MS patients members of MS societies all over Greece completed the Greek version of MSISQ-15 along with demographic data. The sample of 866 participants was composed by 66.5% of women and 33.5% of men. SD was present in both sexes in high levels with women having higher scores in Primary SD and men having higher scores in the other two subscales. For the case of Primary SD there was a collective significant effect between Gender, Age and duration of MS, and prevalence of SD. The same stands for the case of Secondary SD. In the case of the Tertiary SD, Gender was the only significant predictor of prevalence of SD. Results of the regression model for the total Score of SD revealed a significant positive relation between Age and MS Duration with the prevalence of SD. Also, there was a strong negative effect on prevalence of SD moderated by Age and MS Duration. SD is present in Greek MS patients in high rates in both sexes with age, MS duration and gender being the main predictors. Awareness of SD in patients with MS is essential for successful evaluation and management. Clinicians working with MS should proactively ask their patients about their sexual life in order to provide suggestions and solutions about these issues or a referral to a sex specialist.

Comparative Study of Individuals with and Without Multiple Sclerosis: Overall Profile of Quality of Life, Exercise, Health Behaviors

Multiple Sclerosis (MS) patients differ with healthy populations in quality of life parameters, physical activity participation and health behaviors. However, no research has been conducted yet comparing such differences, outlining an overall profile. The purpose of this study was to examine and compare the profile of Greek MS patients with healthy individuals, as regards to the quality of life, physical activity involvement, adoption of health behaviors, and levels of depression and anxiety. The sample consisted of 26 MS patients and 90 healthy individuals overall 116 participants. Instruments used included the GLTE Questionnaire, habitual physical activity questionnaire, the SF 36, the Fagerstrom Test for Nicotine Dependence, the Hospital Anxiety and Depression Scale, the Baecke and the Nutritional Behaviors questionnaire. T-test for independent variables was used to locate differences between individuals with or without MS and according to gender. Significance level was set at p <.05. The results showed MS patients as choosing light physical activity (PA) levels compared to healthy participants choosing moderate levels of PA. Healthy individuals also achieved higher scores in leisure time, sport and total physical activity index, exhibiting lower levels of anxiety and depression and better perceived quality of life compared to patients with MS. The profile of MS patients was associated with light PA, lower perceived quality of life, higher anxiety and depression as compared to healthy individuals. Future suggestions were made to examine application of exercise programs and their effect on psychological parameters of individuals with and without MS.

Replication study of GWAS risk loci in Greek multiple sclerosis patients.

To validate in an ethnically homogeneous Greek multiple sclerosis (MS) cohort, genetic risk factors for the disease, identified through a number of previous multi-ethnic genome-wide association studies (GWAS). A total of 1228 MS cases and 1014 controls were recruited in the study, from 3 MS centers in Greece. We genotyped 35 susceptibility SNPs that emerged from previous GWAS or meta-analyses of GWAS. Allele and genotype single locus regression analysis, adjusted for gender and site, was performed. Permutation testing was applied to all analyses. Six polymorphisms reached statistical significance (permutation p value < 0.05). In particular, rs2760524 of LOC105371664, near RGS1 (permutation p value 0.001), rs3129889 of HLA-DRA, near HLA-DRB1 (permutation p value < 1.00e-04), rs1738074 of TAGAP (permutation p value 0.007), rs703842 of METTL1/CYP27B1 (permutation p value 0.008), rs9596270 of DLEU1 (permutation p value < 1.00e-04), and rs17445836 of LincRNA, near IRF8 (permutation p value 0.001) were identified as susceptibility risk factors in our group. The current study replicated a number of GWAS susceptibility SNPs, which implies that some similarities between the examined Greek population and the MS genetic architecture of the GWAS populations do exist.

Validation of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) in Greek population with multiple sclerosis

BackgroundCognitive impairment is experienced by about 50% of patients with Multiple Sclerosis (MS) worldwide and affects their employment, disease management and quality of life in general. The Brief International Cognitive assessment for MS (BICAMS) is a brief, practical and potentially universal battery for cognitive impairment in MS patients. It consists of three tests: the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test-2 (CVLT-2) and the Brief Visuospatial Memory Test-Revised (BVMT-R). ObjectiveThe objective of this study was to validate the BICAMS in Greek MS patients and controls. MethodsForty four MS patients and seventy nine healthy control (HC) participants were recruited and tested. They were group matched for age, education, gender and also premorbid cognitive reserve. All of them completed the three tests of the BICAMS battery. Instead of CVLT-2, the Greek validated form (Greek Verbal Learning Test, GVLT), was used. In addition, cognitive reserve was assessed using the Cognitive Reserve Index questionnaire (CRIq) standardized for the Greek population. ResultsSignificant difference was found in the performance of the two groups in all tests (p<0.0001, p<0.02, p<0.009 for SDMT, GVLT and BVMT-R respectively). Test-retest reliability was good for all the tests. Based on the criterion of 1 or more tests below the 5th percentile of healthy controls performance, 47% of patients were found impaired. ConclusionsThe study provides validation of BICAMS in Greek population and therefore facilitates the use of this battery in clinical practice and in future studies of MS patients in Greece.

Sequencing analysis of the human glucocorticoid receptor (NR3C1) gene in multiple sclerosis patients

Various specific human glucocorticoid receptor (NR3C1) gene polymorphisms have been described in multiple sclerosis (MS) patients and correlated with disease progression, susceptibility and aggressiveness. Herein, we investigated the presence of gene alterations in the entire coding region of the NR3C1 in MS patients of variable clinical status (CIS, RRMS and SPMS) and the association(s) of these alterations with severity of disease (EDSS), response to glucocorticoid (GC) treatment and clinical improvement. Sixty Caucasian Greek MS patients were included. Sequencing the coding sequences and intron-exon boundaries of the NR3C1 did not reveal the presence of mutation(s) in any of the MS patients. Three previously described polymorphisms were detected: p.N363S (rs6195), p.N766N (rs6196) and c.1469-16G>T (rs6188). None of the identified alleles/genotypes were found to be associated with the severity of disease, response to glucocorticoids and disease subtypes. Known polymorphism, such as ER22/23EK that has been previously detected in MS patients, was not detected. There is a considerable ethnicity-related variation in the frequency of the NR3C1 polymorphisms. Although a genetic basis of the glucocorticoid sensitivity exists in healthy population, in the presence of chronic inflammation and abundance of cytokines - such in MS patients - other factors appear to play a more important role in GC sensitivity.

Prevalence of cerebrospinal fluid oligoclonal IgG bands in Greek patients with clinically isolated syndrome and multiple sclerosis

Lower prevalence of cerebrospinal fluid oligoclonal IgG bands (IgG-OCBs) has been reported in multiple sclerosis (MS) patients from Southern Europe compared to other western countries. ObjectivesWe aimed to determine the prevalence of CSF OCBs in Greek MS patients and to examine their relation with some selected clinical and demographical features. MethodsIncluded patients fulfilled the 2005 McDonald criteria for definite MS (CDMS) or clinically isolated syndrome (CIS) and had a spinal tap performed between 2006 and 2010. Paired CSF and plasma samples were analyzed using isoelectric focusing followed by IgG-specific immunofixation. A pattern of two or more bands present only in the CSF was defined as positive. OCB status was correlated with age at disease onset, initial symptomatology, relapse rate, disease subtype, disease duration, medication, EDSS score and MSSS. ResultsOf the 231 included patients (53.2% with CDMS and 48.6% with CIS) 67.5% had OCBs. The prevalence of positive patterns did not differ between CIS and CDMS patients (67.6% vs. 67.5%, respectively). OCB-positive patients were younger than OCB-negative patients (35.2±10.3 vs. 38.7±11.8 years respectively, p=0.022) and had more frequently cervical spinal cord lesions (x2=7.08, p=0.008). No difference was observed between the two subgroups in the other studied disease parameters. ConclusionDespite the lower frequency of positive IgG-OCB patterns in our patients, both subgroups were mostly similar with regard to their clinical and demographic characteristics suggesting that the OCB status lacks prognostic significance in MS.

Plasma homocysteine levels in patients with multiple sclerosis in the Greek population

BackgroundIn recent years, there has been increasing interest in the role of plasma homocysteine (Hcy) as a possible risk factor for several diseases of the central nervous system. The aim of this study was to determine the plasma levels of Hcy in a group of multiple sclerosis (MS) patients from a Greek population and the possible correlation with age, disability status, activity or duration of disease, sex, and treatment. MethodsThe MS group that was studied consisted of 46 patients and a total of 42 healthy individuals served as a control group. Plasma Hcy levels were determined by means of high-performance liquid chromatography coupled with fluorescence detection, after precolumn derivatization with 4-Fluoro-7-aminosulfonylbenzofurazan (ABD-F). ResultsStatistical analysis revealed that, in the MS patients, Hcy levels were not significantly different as compared to those in the controls. Men presented with higher Hcy levels than women in the MS group; however, age, disease subtype, disease duration, relapse rate, and Expanded Disability Status Scale score/Multiple Sclerosis Severity Score did not significantly affect Hcy levels in MS patients. ConclusionThe preliminary data suggest that Hcy levels were not elevated in our sample of Greek MS patients, which does not support previous findings of a significant correlation between elevated serum Hcy levels and MS. Further studies to establish a possible association between MS and Hcy levels in the context of different ethnic groups with different habits are needed.

Validity and reliability of the FSS in Greek MS patients

ObjectivesThe study provided validity and reliability evidence of the Fatigue Severity Scale (FSS) in Greek patients with multiple sclerosis (MS).Materials and MethodsThe FSS was administered to 72 MS patients, without co morbid fatigue and 75 matched paired controls with respect to gender and age. Both groups responded to the FSS, SF-36v2, BDI-II and a demographic questionnaire on two time points separated by a 1-week interval. Exploratory and confirmatory factor analysis was performed to test construct validity, concurrent and divergent validity, internal and test-retest reliability were also examined.ResultsExploratory and confirmatory factor analysis, intercorrelations with BDI-II (r = 0.552, p < 0.01) and SF-36v2 vitality (r = −0.715, p < 0.01) and physical functioning (r = −0.673, p < 0.01) subscales, and differences between patients and non patients (t(145) = 6.007, p < 0.001), revealed sufficient construct, concurrent and divergent validity evidence. The factor analysis demonstrated a unidimensional structure Cronbach alpha (0.953) and ICC (0.889) was high, indicating that the responses of our sample were internally consistent and stable across time.ConclusionThe Greek version of FSS is valid and reliable and may be used by clinicians and researchers to assess fatigue of Greek MS patients.

The rs10492972 KIF1B polymorphism and disease progression in Greek patients with multiple sclerosis

A recent genome-wide association study (GWAS) demonstrated an association of the rs10492972[C] variant of KIF1B with multiple sclerosis (MS) [1]. KIF1B encodes a kinesin superfamily member involved in mitochondrial axonal transport and may influence the ability of oligodendrocytes to remyelinate demyelinated axons [2, 3]. Impaired mitochondrial transport and chronic demyelination have been linked to axonal loss, which is important in the development of irreversible disability in MS [2, 4]. We therefore sought to investigate a possible influence of rs10492972 on disease progression in Greek MS patients. We studied 609 patients with MS [5]. Demographic and clinical data are shown in the table. Expanded disability status scale (EDSS) was measured in remission [6]. A total of 243 patients received disease-modifying therapy. MS severity score (MSSS) was determined in 562 patients (disease duration[1 year) [7]. The control group consisted of 230 healthy subjects (mean age 38.1 ± 10.7 years, 121 women). Patients and controls gave written informed consent for molecular genetic studies. DNA was isolated from peripheral blood using standard NaCl extraction. Genotyping of rs10492972 was performed with a standard PCR protocol (primers: 50 GGATACAAGGGGTGGTGA 30, 50 AAGTTATGTGGCCAGGA 30). MboII restriction of the 112-bp product resulted in Tand C-alleles (T-allele: 67 and 45-bp products; C-allele: 112-bp product). Statistical comparisons between patients and controls and between patients with different genotypes were performed using Chi-square, ANOVA, Mann–Whitney, and Kruskal–Wallis tests, as appropriate. Kaplan–Meier analysis (log-rank test) was used to assess the effect of genotypes on time to sustained disability. Analysis was performed with SPSS software. Genotype distribution in patients and controls was in Hardy–Weinberg equilibrium (p = 0.31 and 0.65). C-allele frequency was 0.31 in both patients and controls. There was no difference in allelic or genotype frequencies between patients and controls (p = 0.99 and 1.0). MSSS and time to EDSS 4.0 (Fig. 1) or 6.0 were not significantly

Interleukin-1B and interleukin-1 receptor antagonist gene polymorphisms in Greek multiple sclerosis (MS) patients with bout-onset MS

We investigated the association of specific polymorphisms of the interleukin IL-1b (AvaI -511 and TaqI +3,953) and IL-1 receptor antagonist (IL-1RN) (a variable number of tandem repeats; VNTR) genes with both the susceptibility to and the clinical characteristics in Greek multiple sclerosis (MS) patients cohort with bout-onset. Genotypes were determined from 351 patients with clinically definite MS and 375 age- and sex-matched healthy controls. Our results showed no significant differences in the distribution of these polymorphisms between MS patients and controls. Furthermore, stratification for clinical characteristics, such as age at disease onset, clinical course, sex, and severity did not provide significant differences between patients and controls. Together, our findings suggest that IL-1B and IL-1RN gene polymorphisms may not be relevant to the susceptibility to MS or the clinical characteristics of Greek MS patients.

Validity and Reliability of the Greek Version of the Multiple Sclerosis International Quality-of-Life Questionnaire

Background and PurposeThere are no data regarding psychometrically validated, health-related quality-of-life instruments designed specifically for patients with multiple sclerosis (MS) in Greece. Recently, the MS International Quality-of-Life questionnaire (MusiQoL), a multidimensional, self-administered questionnaire, which is available in 14 languages (including Greek), has been validated using a large international sample. We investigated the validity and reliability of the Greek version of the MusiQoL.MethodsConsecutive patients with different types and severities of MS were recruited from two tertiary-care centers in Greece. All patients completed the MusiQoL, the Short-Form-36 quality-of-life questionnaire (SF-36), and a symptom checklist at baseline and 21±7 days (mean±SD) later. Data regarding sociodemographic status, MS history, and functional outcome were also collected prospectively. Construct validity, internal consistency, reproducibility, and external consistency were tested.ResultsA total of 92 patients was evaluated. The construct validity was confirmed in terms of satisfactory item-internal consistency correlations and scaling success (87.5-100%) of item-discriminant validity. The dimensions of the MusiQoL exhibited high internal consistency (Cronbach's alpha: 0.63-0.96), and reproducibility was satisfactory (intraclass correlation coefficients: 0.69-0.99). External validity testing indicated that the MusiQoL correlated significantly with all SF-36 dimension scores (Spearman's correlation: 0.43-0.76).ConclusionsThe Greek version of the MusiQoL appears to be a valid and reliable instrument for measuring quality of life in Greek MS patients.

APOE genotypes in Greek multiple sclerosis patients: no effect on the MS Severity Score

APOE genotypes in Greek multiple sclerosis patients: no effect on the MS Severity Score

Disclosing the diagnosis of multiple sclerosis

The question of how best to disclose to patients the diagnosis of serious and/or incurable neurological diseases has been much explored, but that of when has received little rigorous study. The present study investigates this question in relation to multiple sclerosis (MS), a disease marked by its incurability, unpredictability and predilection for young adults. We aimed to ascertain the preferences of Greek MS sufferers concerning when they should ideally be informed they have the disease, and their preferences and reactions regarding disclosure of the diagnosis. Design, setting and patients 1,200 Greek MS patients,members of the MS Society, were asked to complete a questionnaire regarding their experience of and attitudes towards receiving the diagnosis. 1,200 Greek MS patients,members of the MS Society, were asked to complete a questionnaire regarding their experience of and attitudes towards receiving the diagnosis. 657 patients (55 %) responded. 91% favoured learning the diagnosis immediately, but only 44% had had this experience: 29% had been informed within 1-3 years, and 27% later. Interestingly, however, a significant minority (9 %) suggested a possible preference for delayed delivery of diagnosis and 23.2% stated that concealing the diagnosis would not lead to loss of confidence in their doctor. This study-the largest of its kind-provides objective data supporting prompt disclosure of diagnosis as the clearly-expressed preference amongst most patients. Interestingly, however, the results also re-emphasise the importance of a difficult medical art: attempting to judge whether an individual patient is one (of the 91%) preferring immediate disclosure-or of the nearly 1-in-10 (9%) who may not.