Fatigue, depression and disability accumulation in multiple sclerosis: a cross-sectional study

Objective:  To investigate the influence of disability and the speed of disability accumulation on fatigue and depression in a large cohort of patients with multiple sclerosis (MS).
Methods:  A total of 412 patients completed the Fatigue Severity Scale (FSS) and Center for Epidemiological Studies Depression Scale (CESD). The patients were registered at our outpatient department and demographic and disease specific data were compared between patients with and without severe fatigue (FSS ≥ 5.0) and clinically significant depressive symptoms (CESD ≥ 16). We investigated the association of Expanded Disability Status Scale (EDSS) scores, multiple sclerosis severity scores (MSSS) and either CESD scores or FSS-scores with severe fatigue and clinically significant depressive symptoms in a multivariable logistic regression model, with adjustment for possible confounders.
Results:  Only CESD scores were independently associated with severe fatigue. FSS scores and female gender were independently associated with clinically significant depressive symptoms. Neither EDSS nor MSSS scores were independently associated with fatigue or depression.
Conclusion:  In patients with MS, fatigue and depression are strongly associated with each other but not with the degree of disability or the speed of disability accumulation.     

Apolipoprotein E genotype does not associate with disease severity measured by Multiple Sclerosis Severity Score

Objectives – During the last years, the association between apolipoprotein E (APOE) polymorphism and disease severity in multiple sclerosis (MS) has been studied with conflicting results. As a result of a considerable individual variation in the clinical course of MS, there is no consensus method for measuring progression using single assessments of disability. Recently, Multiple Sclerosis Severity Score (MSSS) method has been proposed for comparing disease progression using single data. We evaluate in our population if there is any correlation between APOE genotype and severity according to MSSS. Methods – We studied 82 patients followed up in our Neurology Unit throughout the year 2005, diagnosed with MS, and with disease duration of at least 2 years. We collected data concerning demographic and clinical variables including age of onset, disease duration, Expanded Disability Status Scale (EDSS) score and the total number of relapses. When reached, we determined the latency to EDSS scores of 4.0 and 6.0. We calculated progression index (PI) and relapse rate (RR). We ascertained MSSS for our patients in the global MSSS table. Results – We found four patients heterozygous for the E2 allele and 16 for the E4 allele. No patient was homozygous for E2 or E4. RR (P = 0.017 with 95% CI: 0.005–0.57) and PI (P = 0.016 with 95% CI: 0.004–0.38) were significantly lower in E4 carriers. MSSS scores were not associated with carriership of E2 or E4. Conclusion – Our results show no effect of the APOE genotype on the severity of MS measured by MSSS, as a recently published meta‐analysis has noticed. So, our data do not support a role for APOE in MS severity, in spite of the seeming influence shown using other measures such as PI. MSSS is probably the best method to measure severity with a single measure of disability and should be used more frequently when performing genetic research.     

Plasma lipid peroxidation and progression of disability in multiple sclerosis

Oxidative stress has been implicated in the pathophysiology of multiple sclerosis (MS), but its relation to disease progression is uncertain. To evaluate the relationship of plasma lipid peroxidation with progression of disability in MS, we measured blood plasma fluorescent lipid peroxidation products (PFLPP) levels in 23 patients with RRMS with a benign course, 32 with secondary progressive MS, 24 with primary progressive MS and 30 healthy controls. None of the patients had a relapse within the previous 3 months. Progression of disability was evaluated during a follow-up period of 5 years by the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Severity Score (MSSS). We found plasma PFLPP levels elevated in patients with MS compared with controls ( P  < 0.0001), but there was no difference between patients with a benign and progressive disease course. There was no correlation between PFLPP levels and worsening of disability on the EDSS and speed of progression on the MSSS. Our data suggest that there is no relation between the degree of oxidative stress in plasma and progression of disability in MS.     

T2 lesions and rate of progression of disability in multiple sclerosis

Background and purpose: To assess the predictive value of T2 lesions on the rate of progression of disability in multiple sclerosis (MS). Methods: We reanalyzed T2 lesion number and load on brain MRI scans, performed before 1997, of 186 MS patients, who were clinically followed. There were 90 patients with progressive MS (35 secondary progressive and 55 primary progressive), and 96 with relapsing remitting MS. The rate of progression of disability was measured by time to sustained progression of disability (defined as an increase in ≥ 1 point when the Expanded Disability Status Scale (EDSS) was 5.5 or less and an increase in EDSS of ≥ 0.5 point when the EDSS was 6.0 or higher), and by the Multiple Sclerosis Severity Score (MSSS). Results: During follow‐up (median 15 years, IQR 12–17 years), 94% of the patients with progressive MS and 50% of the patients with relapsing remitting MS had progression of disability. Higher T2 lesion number and load were modestly associated with a higher rate of disease progression on the MSSS and a shorter time to progression of disability in relapsing remitting MS, but not in progressive MS. Conclusions: Our findings indicate that the amount of T2 lesions has a small predictive value for progression of disability in relapsing remitting MS, but has no influence on the rate of progression in progressive MS.     

Natural history of multiple sclerosis in a population-based cohort

Background and purpose:  We sought to identify predictive clinical factors of disability during initial course in multiple sclerosis (MS) patients.
Methods:  A total of 2871 MS patients from the LORSEP (Lorraine Multiple Sclerosis) population-based cohort were analyzed. The relationships between baseline demographic, clinical predictors and time to assignment of Expanded Disability Status Scale (EDSS) scores of 3, 4 and 6 were assessed using a Cox regression model.
Results:  Multivariate analysis showed that, for relapsing–remitting patients, a shorter time to assignment of an EDSS score of 4 was associated with an older age of onset of MS and incomplete recovery from the first relapse. Median times were not influenced by gender or the time between the first two relapses. The results also demonstrated that MS progression is independent of the initial clinical data once an EDSS score of 4 is reached rather than a score of 3 because the time from EDSS 3 to assignment of EDSS 4 were correlated with predicting variables. The data were very different for the time between assignment of scores of 4 and 6 because the median times were not influenced by any of the predicting variables.     

Association of apolipoprotein E and myeloperoxidase genotypes to clinical course of familial and sporadic multiple sclerosis

The importance of apolipoprotein E (ApoE) and myeloperoxidase (MPO) genotypes in the clinical characteristics of multiple sclerosis (MS) has been recently emphasized. In a large group of Polish patients we have tested the hypothesis that polymorphism in ApoE and MPO genes may influence the course of the disease. Genotypes were determined in 117 MS patients (74 females and 43 males; 99 sporadic and 18 familial cases) with mean EDSS of 3.6, mean age of 44. 1 years, mean duration of the disease 12.8 years and mean onset of MS at 31.2 years, and in 100 healthy controls. The relationship between ApoE and MPO genes' polymorphism and the MS activity as well as the defect of remyelination (diffuse demyelination) and brain atrophy on MRI were analysed. The ApoE epsilon4 allele was not related to the disease course or the ApoE epsilon2 to the intensity of demyelination on MRI. The genotype MPO G/G was found in all familial MS and in 57% (56/99) of sporadic cases. This genotype was also related to more pronounced brain atrophy on MRI. The MPO G/G subpopulation was characterized by a significantly higher proportion of patients with secondary progressive MS (P < 0.05) and by a higher value of EDSS. According to our results the MPO G allele is frequently found (in 96% of cases) among Polish patients with MS. More severe nervous tissue damage in the MPO G/G form can be explained by the mechanism of accelerated oxidative stress. It seems that MPO G/G genotype may be one of the genetic factors influencing the progression rate of disability in MS patients.     

Insulin‐like growth factor (IGF)‐I and IGF‐binding protein‐3 serum levels in relapsing–remitting and secondary progressive multiple sclerosis patients

Background: Insulin‐like growth factor (IGF)‐I has a role in remyelination, and insulin‐like growth factor‐binding protein‐3 (IGFBP‐3) might reduce its bioavailability. A role of IGFBP‐3 in multiple sclerosis (MS) progression was hypothesized in patients with primary progressive (PP) MS. Objective: To evaluate serum levels of IGF‐I and IGFBP‐3 in patients with relapsing–remitting (RR) and secondary progressive (SP) MS and their correlations with disease activity and progression. Methods: Sixty‐three (41 RR and 22 SP) ‘naive’ MS patients and 60 age‐matched healthy controls were enrolled. Patients were assessed through clinical [Expanded Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), number of relapses] and laboratory investigations. IGF‐I and IGFBP‐3 were measured by ELISA. Results: Levels of IGF‐I and IGFBP‐3 were similar in the two MS groups. IGFBP‐3 levels were higher in patients with MS than in controls (P < 0.001), with a reduction in IGF‐I/BP3 ratio (P < 0.001). Patients showing IGFBP‐3 levels higher than 2SD of the normal population had a higher EDSS (mean EDSS 3.7 vs. 2.8, P = 0.021). MSSS was not related to IGF‐I or IGFBP‐3 serum levels. Conclusions: Our patients showed high IGFBP‐3 serum levels respect to controls and higher serum levels were associated with a higher EDSS, despite of comparable disease duration. Therefore, MS and higher disability seem to be associated with a reduction in bioavailability of IGF‐I. MSSS score was not related to IGFBP‐3 levels, suggesting that IGFBP‐3 might not have the pathogenetic role previously suggested for PP MS, in the mechanism of progression in the SP form of disease.     

Alcohol, coffee, fish, smoking and disease progression in multiple sclerosis

Background: Certain lifestyle factors might influence disease activity in multiple sclerosis (MS). Objectives: To investigate the consumption of alcoholic beverages, caffeinated drinks, fish and cigarette smoking in relation to disability progression in relapsing onset and progressive onset MS. Methods: We conducted a cross‐sectional survey amongst individuals with MS, registered by the Flemish MS society in Belgium. A time‐to‐event analysis and Cox proportional‐hazard regression were performed with time to Expanded Disability Status Scale (EDSS) 6 (requiring a cane or support to walk for a distance of 100 m) as outcome measure. Hazard ratios for the time from onset and from birth were adjusted for age at onset, gender and immunomodulatory treatment. Results: Data of 1372 persons with definite MS were collected. In the relapsing onset group, a decreased risk for reaching EDSS 6 was found in regular consumers of alcohol, wine, coffee and fish compared with those who never consumed these substances. Cigarette smoking was associated with an enhanced risk for reaching EDSS 6. In the progressive onset group, no association with the risk of reaching EDSS 6 was found, except for the type of fish. Preference for fatty fish was associated with an increased risk to reach EDSS 6, when lean fish was taken as the reference category. Conclusion: Consumption of alcoholic beverages, coffee and fish were inversely associated with progression of disability in relapsing onset MS, but not in progressive onset MS. These findings allow to support the hypothesis that different mechanisms might underlie progression of disability in relapsing and progressive onset MS.     

No association of apolipoprotein E epsilon4 genotype with faster progression or less recovery of relapses in a Spanish cohort of multiple sclerosis

BACKGROUND: Recent data have suggested a faster deterioration of multiple sclerosis (MS) patients who harbour the epsilon4 allele of the apolipoprotein E (APOE) gene. We investigate the relationship of APOE genotypes with disease severity and clinical recovery of relapses in a MS population of the north of Spain. METHODS: One hundred and thirty-three patients with clinically defined MS were studied. Disease course (relapsing versus progressive), age of onset, duration of the disease and disability measured by the Expanded Disability Status Scale (EDSS) were recorded. Worsening was measured by the Progression Index (PI) and by EDSS 4 and 6 latencies. In 79 patients with relapsing-remitting (RR) MS the degree of clinical recovery of relapses (total versus partial) was assessed. RESULTS: The frequency of the APOE epsilon4 allele in our patients was similar to that found in other southern European populations. APOE epsilon4 patients did not have a faster progression as assessed by PI and EDSS 4 and 6 latencies. Among 79 patients with RRMS there were no significant differences in the degree of recovery of relapses. CONCLUSIONS: In this MS population, APOE epsilon4 polymorphism is not associated with a more severe clinical course and does not appear to influence recovery of exacerbations.     

Multiple sclerosis patients with anti-lipid oligoclonal IgM show early favourable response to immunomodulatory treatment

Background and purpose:  Interferon beta and Glatiramer acetate are safe immunomodulatory treatments (IT) for multiple sclerosis (MS), but not always effective. New drugs are available, although they show more side-effects and unknown long-term safety profile. Anti-lipid oligoclonal IgM bands (OCMB) distinguish MS patients with early aggressive course. We prospectively studied if IT are effective in these patients or if they are candidates for more aggressive drugs as first therapeutic option.
Methods:  Seventy-five clinically isolated syndrome patients were studied. OCMB and conversion to MS were assessed. Patients suffering at least two demyelinating events within 3 years were considered eligible to start IT.
Results:  Eighteen patients showed OCMB (M+) and 57 lacked them (M−). All M+ patients and only 25 M− patients were treated. The other 32 M− patients suffered less MS attacks than those required to initiate treatment. IT similarly reduced relapse rate in both treated groups ( P  < 0.0001) and reduced Expanded Disability Status Scale (EDSS) progression in M+ patients, whose EDSS score had significantly increased before treatment. EDSS did not change in M− patients during follow-up, regardless if they were treated or not.
Conclusions:  Oligoclonal IgM bands identify MS patients who are candidates for early immunomodulatory treatment as IT improves their initial aggressive disease course.     

Multiple sclerosis and cognitive decline: is ApoE‐4 a surrogate marker?

Carmona O, Masuet C, Santiago O, Alía P, Moral E, Alonso‐Magdalena L, Casado V, Arbizu T. Multiple sclerosis and cognitive decline: is ApoE‐4 a surrogate marker?
Acta Neurol Scand: 2011: 124: 258–263.
© 2011 John Wiley & Sons A/S. Background – The role of the apolipoprotein E (ApoE) polymorphism has been well demonstrated in neurodegenerative disorders such as Alzheimer. However, its role in multiple sclerosis (MS) remains unclear. Aims – The aims of our study were as follows: (i) to assess whether ApoE‐4 might be a surrogate marker of cognitive decline in MS; (ii) to confirm the presence of cognitive impairment in mildly disabled patients treated with interferon‐beta; and (iii) to analyse the correlation between cognitive disturbances and clinical variables. Material and methods – Fifty relapsing‐remitting MS patients underwent a battery of neuropsychological tests and were genotyped for ApoE. Their scores were compared with those of 35 controls. Results – No association was found between ApoE‐4 and cognitive impairment. Significant differences in most domains were observed between MS and the control group. Cognitive decline was not related to disability progression. Conclusion – No association between cognitive impairment and ApoE‐4 or clinical markers was detected in our MS patients.     

No major association of ApoE genotype with disease characteristics and MRI findings in multiple sclerosis

BACKGROUND: Whereas a number of studies suggest that the ApoE polymorphism is not associated with disease susceptibility in multiple sclerosis (MS), results with regard to disease severity, however, are conflicting. Some studies suggest an unfavourable role of the epsilon4 allele. This study was performed to assess the association of the ApoE polymorphism with both disease susceptibility and disease course in a large group of MS patients using clinical and MRI measures. In addition the data were combined with available data from the literature. METHODS: In a group of 408 patients with clinically definite MS, genotype distribution was compared with that of 144 healthy controls. Combined analysis of published data on the association of ApoE polymorphism with MS was performed. Demographic and clinical findings were recorded and related to the ApoE genotype. In a subgroup, longitudinal MRI findings were available and related to the ApoE genotype. RESULTS: No significant differences were found in the distribution of genotypes between MS patients and controls. Combined analysis of published data showed a slightly increased susceptibility for MS in epsilon2-carriers. Disease characteristics (including age at onset and onset type), disease severity (progression index, time to reach EDSS 6) and MRI findings (lesion volumes and atrophy measures) were not associated with carriership o epsilon2 or epsilon4. CONCLUSIONS: In this cohort no association of the ApoE genotype with disease susceptibility nor clinical and MRI measures could be identified. However, combined analysis of published data could not definitely exclude the possibility of a minor role for epsilon2-carriership in MS.     

The HLA-DRB1 and HLA-DQB1 alleles are associated with multiple sclerosis disability progression in Slovak population

Objective: The aim of our present study was to analyse the association of HLA-DRB1 and -DQB1 alleles and genotypes with Multiple Sclerosis (MS) disability progression in a cohort of Central European Slovak population.

Methods: The allele and genotype variants were analyzed in 282 non-related MS patients. Rate of disease disability progression was evaluated using EDSS score in the 5^th, 7^th, 10^th, and 15^th year of disease duration, time to reach EDSS score 3 and 5, and MSSS score. Genotyping was performed by polymerase chain reaction with sequence-specific primers.

Results: We found that carriers of homozygous genotype for alleles DRB1*15 and DQB1*03 reached EDSS score 3 significantly earlier than non-carriers of these alleles (p = 0.0172; p = 0.00183, respectively). Genotype DQB1*03/03 carriage was also associated with significantly reduced time to reach EDSS score 5 (p = 0.00316). Lower EDSS score in the 5^th year of disease duration was found in carriers of DRB1*07 allele (p _cor = 0.028). When MSSS score was used, genotype DRB1*15/15 was found to be less frequent in slow progressing MS patients, when compared to MS patients with mid-rate and rapid disease disability progression (p _cor = 0.0305).

Discussion: We showed for the first time that HLA-DRB1 and -DQB1 genotypes are genetic markers associated with disability progression in Slovak MS patients. Genotypes DRB1*15/15 and DQB1*03/*03 were identified as short-term clinical negative prognostic factors, while allele DRB1*07 carriage appeared to be a positive prognostic marker of better MS outcome.     

Cytotoxic T lymphocyte associated antigen-4 exon 1 A/G polymorphism in Iranian patients with multiple sclerosis

Background:  Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a T-cell surface receptor of activated T cells.
Material and methods:  We studied 100 Iranian patients with clinically definite multiple sclerosis (MS) and 100 ethnic, sex- and age-matched controls. CTLA-4 exon 1 A/G polymorphism was compared amongst patients and controls.
Results:  There was no statistically significant difference in the allelic [odds ratio (OR): 1.19, confidence interval (CI) 95%: 0.76–1.85, P  = 0.4] and genotypes (OR: 1.60, CI 95%: 0.911–2.824, P  = 0.102) distribution amongst patients and controls. Also gender, course and progression index did not reveal any statistically significant differences in allele and genotype distribution of A/G polymorphism.
Conclusion:  As a non-European patient population, our results are consistent with the major previous studies showing no significant associations between CTLA4 exon 1 polymorphism and neither MS nor any of its subtypes.     

Disability Progression in Multiple Sclerosis Is Affected by the Emergence of Comorbid Arterial Hypertension

MethodsThis was a retrospective study of 2,813 patients who were followed for 20 years. We modeled the associations of several risk factors with the pattern of disability progression. The primary end point was the rate of disability progression.ResultsIn total, 2,396 patients were available for analysis, of which 1,074 (44.8%) scored 4 (EDSS4) on the Expanded Disability Status Scale (EDSS), 717 (29.9%) scored 6 (EDSS6), and 261 (10.9%) scored 8 (EDSS8). The mean times to reach scores of 4, 6, and 8 were 123.5, 163.1, and 218.9 months, respectively. Hypertension was present in 207 (8.6%) patients during follow-up. Hypertension was associated with a higher probability of reaching each EDSS score compared to non-hypertensive patients: 62% vs. 43% for EDSS4 (p<0.01), 51% vs. 28% for EDSS6 (p<0.01), and 17% vs. 10% for EDSS8 (p<0.01). Nevertheless, hypertensive MS patients experienced longer intervals to reach each EDSS score: longer by 51.6, 38.9, and 62.7 months to EDSS4, EDSS6, and EDSS8, respectively (p<0.01) when compared to non-hypertensive MS patients reaching the same EDSS scores.ConclusionsDisability progression is more prevalent amongst hypertensive MS patients. However, they experience longer time intervals between the stages of disability progression.     

Prevalence of migraine, tension-type headache and trigeminal neuralgia in multiple sclerosis

Background:  Prevalence rates of headache in multiple sclerosis (MS) patients varied widely in recent studies. This study aimed to investigate the 1 year prevalence of headache in MS compared with the general population.
Methods:  Population-based case–control study in Germany.
Results:  We included 491 patients with definite MS (68% female, mean age 45.3 years, 63.7% relapsing remitting MS, mean Expanded Disability Status Scale (EDSS) 3.2, 106 treated with interferon-β, 53 with glatiramer acetate, 271 untreated) and 447 age and gender matched controls. Headache was diagnosed with a validated questionnaire according to the International Headache Society Criteria. Headache prevalence was 56.2% (tension type headache 37.2%, migraine 24.6%). Headache prevalence rates did not differ from controls. Headache was not associated with disability or treatment. Trigeminal neuralgia was found in 6.3% of MS cases.
Conclusion:  Results suggest that headache in MS patients reflects comorbidity in most conditions.     

Efficacy of natalizumab in second line therapy of relapsing–remitting multiple sclerosis: results from a multi-center study in German speaking countries

Background:  Natalizumab has been recommended for the treatment of relapsing–remitting multiple sclerosis (RRMS) in patients with insufficient response to interferon-beta/glatiramer acetate (DMT) or aggressive MS. The pivotal trials were not conducted to investigate natalizumab monotherapy in this patient population.
Method:  Retrospective, multicenter study in Germany and Switzerland. Five major MS centers reported all RRMS patients who initiated natalizumab ≥12 months prior to study conduction.
Results:  Ninety-seven RRMS patients were included [69% female, mean age 36.5 years, mean Expanded Disability Status Scale (EDSS) 3.4; 93.8% were pre-treated with DMT], mean treatment duration with natalizumab was 19.3 ± 6.1 months. We found a reduction of the annualized relapse rate from 2.3 to 0.2, 80.4% were relapse free with natalizumab. EDSS improved in 12.4% and 89.7% were progression free (change of >/= 1 EDSS point). Eighty-six per cent of patients with highly active disease (>/= 2 relapses in the year and >/= 1 Gadolinium (Gd)+ lesion at study entry, n  = 20) remained relapse free. The mean number of Gd enhancing lesions was reduced to 0.1 (0.8 at baseline). Discontinuation rate was 8.2% (4.1% for antibody-positivity).
Conclusion:  Natalizumab is effective after insufficient response to other DMT and also in patients with high disease activity.     

Preliminary observations on APOE epsilon4 allele and progression of disability in multiple sclerosis

BACKGROUND: Apolipoprotein E expression is increased in regenerating neural tissue and the APOE epsilon4 allele is associated with impaired neuronal repair. Since repair is essential for the restoration of central nervous system function following multiple sclerosis (MS) relapses, APOE genotype may influence clinical progression of the disease. OBJECTIVE: To examine the association of the APOE genotype with disease susceptibility and progression in MS. PATIENTS AND METHODS: APOE genotyping was determined by polymerase chain reaction and restriction enzyme digestion in 47 patients with MS who had been followed up every 3 months for 2 years as part of an open-label clinical trial with glatiramer acetate. The Expanded Disability Status Scale (EDSS) was used to assess clinical progression. RESULTS: Nine patients were heterozygous and 1 patient was homozygous for the APOE epsilon4 allele, for a frequency of 12% (11/94), which is similar to that of the general Israeli population. The APOE epsilon4 carriers had a mean +/- SE EDSS score of 3.10+/-0.45 at entry, which was not significantly different from the remaining 37 patients (2.62+/-0.25). During the observation period, the EDSS score of the APOE epsilon4 carriers deteriorated to 4.00+/-0.63 while the other patients remained stable with an EDSS score of 2.74+/-0.31. The interaction of genotype with disability over time was significant (P = .02 by repeated-measures analysis of variance). There were no differences in the number of relapses occurring in the 2 groups. CONCLUSIONS: These preliminary observations suggest that APOE genotype may influence disease progression in MS. The APOE epsilon4 allele was not associated with an increased risk of MS or relapses.     

Quality of life in 1000 patients with early relapsing–remitting multiple sclerosis

Background and purpose:  To examine the quality of life (QoL) in a large cohort of untreated patients with relapsing–remitting multiple sclerosis (RRMS) and to investigate the impact of intramuscular (IM) interferon beta-1a (IFNß-1a) treatment.
Methods:  Prospective, observational, open-label, multicentre study conducted in Germany. Untreated patients with RRMS who initiated treatment with IM IFNß-1a were included and followed for 12 months. QoL was measured using the EQ-5D questionnaire. Clinical response was assessed by relapse rate and disability (Expanded Disability Status Scale; EDSS).
Results:  A total of 1157 patients were included [mean age 37.6 years, median disease duration 13 months, mean relapse rate 1.7 (95%CI: 1.58–1.73), median EDSS score 2.0]. Relapse rate was reduced to 0.6 at 12 months (95%CI: 0.51–0.69, P  < 0.0001). EDSS did not change significantly. At baseline, QoL was considerably lower in MS patients compared with the general German population, but was improved after treatment initiation [utilities of EQ-5D: 0.77 (95%CI: 0.75–0.78) vs. 0.75 (95%CI: 0.74–0.76) at baseline, 95%CI for difference: 0.01–0.03, P  = 0.0046]. Higher disease activity and inability to work were negative predictors of QoL. 14.7% of patients were incapable of working for MS-related reasons.
Conclusions:  Quality of life is considerably impaired in early stages of MS. Treatment initiation with IM IFNß attenuates MS disease activity and improves QoL. Inability to work early during the disease is a major challenge for the social security systems.     

Apolipoprotein E genotype does not influence the progression of multiple sclerosis

Objective: To investigate the association between apolipoprotein E (APOE) polymorphisms and the progression of MS.Methods: We investigated 428 subjects affected by clinically defined MS, with a disease duration of at least three years. We collected data concerning the age at onset of MS, clinical type, disease duration and disability according to the expanded disability status scale (EDSS). We also calculated the progression index (PI) to evaluate disease progression. APOE genotyping and the –491 A/T polymorphism of the APOE promoter were determined.Results: No association was observed between the APOE 4 allele and clinical characteristics of our study population. We also investigated the –491 A/T APOE promoter polymorphism in 236 MS subjects and did not find any association between the –491 A/T polymorphism and the selected clinical variables.Conclusions: In our population the APOE 4 allele and the –491 A/T APOE promoter polymorphism are not associated with a more rapid course of MS.