Health-related quality of life as an independent predictor of long-term disability for patients with relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Predictive factors of long-term disability in patients with relapsing-remitting multiple sclerosis (RR-MS) are well known, but the weight of these factors does not explain the entire change of disability. Few studies have examined the predictive value of quality of life (QoL). OBJECTIVES: To determine the value of the initial level of QoL to predict changes in the disability status of patients with MS and to determine if specific-MS questionnaires predict more accuracy in these changes than generic questionnaires. DESIGN: multicenter, multi-regional, and longitudinal study. Main inclusion criteria: patients with RR-MS subtype and an Expanded Disability Status Scale (EDSS) score lower than 7.0. Sociodemographic and clinical data were recorded at baseline. Every 6 months up to month 24, QoL (MusiQoL and SF-36) was recorded. At 24 months, individuals were defined into two 'disability change' groups: the worsened and not worsened patients. RESULTS: Five-hundred and twenty-six patients were enrolled: 386 (83.7%) not worsened and 75 (16.3%) worsened patients at 24 months. The activity of daily living and the relationship with healthcare workers dimensions of MusiQoL questionnaire were independent predictors of change in the EDSS score after 24 months. The physical-functioning dimension of the SF-36 questionnaire predicted independently disability change after 24 months. CONCLUSIONS: Patient-reported baseline QoL levels provide additional prognostic information on MS disability beyond traditional clinical or sociodemographic factors. These findings reinforce the importance of incorporating a patient's evaluation of their own QoL level during patient monitoring and the assessment of treatment effects.

Validation of the Multiple Sclerosis International Quality of Life questionnaire.

This study aims to validate the Multiple Sclerosis (MS) International Quality of Life (MusiQoL) questionnaire, a multi-dimensional, self-administered questionnaire, available in 14 languages, as a disease-specific quality of life scale that can be applied internationally. A total of 1992 patients with different types and severities of MS from 15 countries were recruited. At baseline and day 21 +/- 7, each patient completed the MusiQoL, a symptom checklist and the short-form (SF)-36 QoL questionnaire. Neurologists also collected socio-demographic, MS history and outcome data. The database was randomly divided into two subgroups and analysed according to different patient characteristics. For each model, psychometric properties were tested and the number of items was reduced by various statistical methods. Construct validity, internal consistency, reproducibility and external consistency were also tested. Nine dimensions, explaining 71% of the total variance, were isolated. Internal consistency and reproducibility were satisfactory for all the dimensions. External validity testing revealed that dimension scores correlated significantly with all SF-36 scores, but showed discriminant validity by gender, socio-economic and health status. Significant correlations were found between activity in daily life scores and clinical indices. These results demonstrate the validity and reliability of the MusiQoL as an international scale to evaluate QoL in patients with MS.

Difference between generic and multiple sclerosis-specific quality of life instruments regarding the assessment of treatment efficacy.

Multiple sclerosis (MS) is a chronic and stressful disease, which significantly affects the quality of life (QoL) of patients. QoL instruments provide information which traditional outcome measures of MS do not. It is unclear if the longer disease-specific instruments provide more useful information than the shorter. We aimed to investigate whether there was any difference between general QoL instrument and MS-specific one on the basis of detecting the efficacy of pulse therapy. 112 clinically definite MS patients were included in the study. Patients enrolled in the study were in relapse period treated by 1 g/day methyl-prednisolone for 5 days. World Health Organization Quality of Life Brief Form, Turkish Version (WHOQoL-BREF-TR) was given as a generic measure and Multiple Sclerosis Quality of Life-54 (MSQoL-54) as an MS-specific measure to assess the QoL. The same scales were administered 1 month after the therapy. MSQoL-54 was correlated with the EDSS in the pre-treatment period but WHOQoL-BREF was not. On day 30, there was a significant increase in both WHOQoL-BREF and MSQoL-54 scores. Increase was more prominent in MSQoL-54. There was a weak correlation between WHOQoL-BREF and MSQoL-54 (r=0.17). Correlation between changes in WHOQoL-BREF and MSQoL-54 scores was even weaker (r=0.11). Correlation between WHOQoL-BREF and EDSS was weaker (r=0.13), and correlation between MSQoL-54 and EDSS was still moderate (r=0.46) when compared with day 0. We concluded that although it takes a longer time to administer, MSQoL-54, as a MS-specific QoL instrument, is favorable and reliable for detecting the QoL not only in the remission but also in the relapse period of MS. Our results also indicated that MS-specific measure of QoL might be used for detecting the treatment effects in relapse period of patients with MS.

Development of multiple sclerosis after vaccination against hepatitis B: a study based on human leucocyte antigen haplotypes.

The aetiology of multiple sclerosis (MS) is still not fully understood. Infectious agents are believed to play a role in the development of this multifactorial disease. Cases in which this disease occurs after administration of both plasma-derived and recombinant hepatitis B vaccines have been reported. In this study, we compared a group of 11 MS patients who developed first clinical symptoms after hepatitis B vaccination (group I) with 71 MS patients who were never vaccinated against hepatitis B and were negative for hepatitis B serology (group II), and 20 healthy controls (group III). Mean age was 27.75 years (19-39) in group I, 30.16 years (18-50) in group II, and 34.4 years (18-50) in group III. Mean attack rate after 2 years was 1.5 in group I and 1.63 in group II. Mean Expanded Disability Status Scale score after 2 years was 1.31 in group I and 1.89 in group II. Human leucocyte antigen (HLA) typing and serology for hepatitis B surface antigen were performed in all groups. In groups I and II, HLA-DR2 was more frequent than in normal healthy subjects. This reflects the general role of HLA in the pathogenesis of MS but suggests that antigen presentation by different HLA is not involved in the development of MS after hepatitis B vaccination. Since there was no difference in the clinical features between vaccinated and nonvaccinated MS patients, this study supports recent reports that hepatitis B vaccination is safe in MS patients and that hepatitis B vaccination is not involved in the development of MS.

Utilization of the auditory consonant trigram test to screen for cognitive impairment in patients with multiple sclerosis: comparison with the paced auditory serial addition test.

Several screening methods have been evaluated, but most of them are insensitive to MS-related cognitive impairment. The Auditory Consonant Trigram (ACT) test, which contains core features required for a working memory task, has been used to test neuro-cognitive function in different samples of patients to examine the status of working memory. The aim of the present study was to investigate the correlation between ACT and the Paced Auditory Serial Addition Test (PASAT), and the usefulness of ACT for evaluating the cognitive impairment in MS in a brief visit A total of 109 consecutive patients with definite MS were included. The patients were administered ACT, PASAT and EDSS. Mean PASAT score and mean ACT score were 46.19 +/- 8.51 and 45.30 +/- 9.07, respectively. Correlations between EDSS and PASAT, and EDSS and ACT were moderately strong. The correlation between ACT and PASAT was very strong (r = 0.831, P < 0.01). The mean time required to perform ACT was significantly shorter than PASAT (7.25 +/- 4.72 and 14.70 +/- 6.97 minutes, respectively). In conclusion, as a relatively brief measure of working memory, ACT was well accepted by MS patients and has a strong correlation with PASAT. Thus, ACT might be used for rapid evaluation of cognitive impairment in patients with multiple sclerosis.

Nitric oxide as an activity marker in multiple sclerosis.

Nitric oxide (NO) molecules have one of the most important roles in the pathogenesis of multiple sclerosis (MS). It has been stated that a continuous and high concentration of NO metabolites in CSF and in the serum of MS patients in relapse may cause toxic damage to myelin and oligodendroglia. The aim of this study was to investigate whether NO is a marker of disease activity and is correlated with other disease activity markers such as active lesions on brain magnetic resonance imaging (MRI) and increased immunoglobulin G (IgG) index. Cerebrospinal fluid (CSF) and peripheral serum (PS) samples were taken from patients with definite MS (n = 24) during relapse and remission and from control subjects (n = 18). The Griess reaction was used to measure the NO metabolites, nitrite and nitrate in CSF and PS. Cranial MRI was carried out with triple dose (0,3 mmol/kg) gadolinium and the IgG index was determined. Nitrite and nitrate concentrations (NNCs) of CSF were 11.16 +/- 8.60 micromol/ml in relapse and 6.72 +/- 3.50 micromol/ml in remission, whereas in PS they were 12.89 +/- 7.62 micromol/ml during relapse and 12.35 +/- 6.62 micromol/ml during remission. In control subjects NNCs in CSF and PS were 7.42 +/- 2.81 micromol/ml and 4.37 +/- 1.63 micromol/ml respectively. NNCs in CSF during relapse period were significantly higher than those of both remission phase and control subjects (p = 0.000). Although serum NNCs did not differ in relapse and remission, they were still higher than normal controls. Validity analysis revealed that NNC measurement in CSF was 71 % specific and 66 % sensitive to disease activity. The most important result was the significant correlation of increased NNCs with the existence of active lesion in cranial MRI and an increase in IgG index (p < 0.05).In conclusion, these results add background data to assist in further outlining the possible role of NO in the pathogenesis of MS. Together with the other markers it may be used as an activity marker in relapses of MS.