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.     

Predictive value of clinical characteristics for 'benign' multiple sclerosis

We studied a cohort of 496 patients who had multiple sclerosis (MS) for at least 10 years. Ten years after disease onset, 151 had benign MS defined as an Extended Disability Status Scale (EDSS) ≤3. Between benign and non-benign patients we compared gender, age at clinical onset, relapsing–remitting or primary progressive, symptoms at onset, recovery from first relapse, time between first and second relapse, number of relapses in the first 5 years, use of immunomodulatory drugs, and EDSS scores at 2, 5 and 10 years. A multivariate regression analysis showed that a relapsing–remitting course, a low EDSS score at 5 years, and a low number of relapses in the first 5 years were predictive for benign MS at 10 years. Other factors had no additional value. Thirty-five of the 51 patients (69%) with benign MS at 10 years were still benign at 20 years. A low 10-year EDSS score was the only clinical variable associated with a benign course at 20 years. Our results suggest that within the first 5 years from onset it is not possible to predict a benign course. Disease course, EDSS score and relapse rate at 5 years are predictors for benign MS at 10 years.     

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 polymorphism interacts with cigarette smoking in progression of multiple sclerosis

Background and purpose:  The influence of apolipoprotein E (ApoE) polymorphism on clinical severity of multiple sclerosis (MS) is still controversial. Cigarette smoking has been suggested to influence the progression of disability in these patients. In this study, we aimed to investigate whether an interaction of smoking with the ApoE polymorphism influences the progression of disability in MS patients.
Methods:  Smoking history from 205 female patients with MS was obtained. Clinical data collected include age at onset, disease duration, annual relapse rate, the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Severity Score (MSSS). ApoE polymorphism was examined in all patients and stratified according to smoking status and associations with the clinical data investigated.
Results:  There were no significant associations between cigarette smoking and any of the clinical characteristics in the whole group of patients. In women carrying the ApoE E4 isoform, smokers had a lower EDSS ( P  = 0.033) and MSSS ( P  = 0.023) in comparison with non-smokers.
Conclusion:  Our data suggest that in women with MS carrying the ApoE E4 isoform, cigarette smoking may have a protective influence on disease progression and accumulation of disability. These findings need to be confirmed by future large longitudinal studies.     

Analysis of the upper urinary tract function in multiple sclerosis patients

Aims –  The objective of this study was to analyse the upper urinary tract (UT) function in a group of consecutive multiple sclerosis (MS) patients, who had not previously been treated by urologist.
Materials and methods –  Ninety-two MS patients suffering from lower UT dysfunction were included in the study. The group of patients consisted of 69 women and 23 men. The average Expanded Disability Status Scale (EDSS) score in our group was 4.29 (0–8.5). Functional examination of the kidneys using assessment of creatinine clearance and morphological examination of the kidneys using ultrasound was performed in all patients. Analysis of the upper UT function is presented.
Results –  The average serum creatinine clearance in our group was 132.84 ml/min/1.73 m² (46.8–510). Lower levels than normal were found in three patients (3.3%). Abnormal ultrasound findings were recorded in five patients (5.4%). The creatinine clearance was correlated with the clinical subtype of MS, the severity expressed by EDSS, the urodynamic parameters, the duration of the disease, the duration of the symptoms of lower UT and the EDSS score. We did not find a statistically significant correlation for any of these parameters.
Conclusions –  Our results suggest that impairment of the upper UT function is exceptional in MS patients.     

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.     

Short-term prognosis in early relapsing-remitting multiple sclerosis

OBJECTIVE: To characterize a group of patients with early MS using prognostic factors and to determine whether these prognostic factors impact on short-term prognosis. METHODS: Data were collected prospectively on 98 patients newly diagnosed with MS in our MS clinic between 1990 and 1998 (average follow-up, 37 months from the time of onset of clinically definite MS [CDMS]). Six prognostic factors were recorded: age at onset, symptoms at onset, MRI status at onset and at diagnosis of CDMS, interval between the first and second attack, attack frequency in the first 2 years, and completeness of recovery from initial attacks. Completeness of recovery was determined using Expanded Disability Status Scale scores (EDSS). Progression was determined by final EDSS and changes in EDSS between initial presentation and final follow-up. RESULTS: Patients predicted to have low risk of progression of MS based on the prognostic factors represented 17% of our patient population (0 to 1 risk factor for progression). The patients with high risk of progression (4 to 6 risk factors) represented 24% of patients. Patients with a high number of risk factors did significantly worse than those with a small or medium number of risk factors in terms of final EDSS and progression to higher EDSS. At the time of diagnosis of CDMS, MRI findings suggestive of MS were seen in 84% of patients (suspicious in 13%, negative in 3%). CONCLUSION: Short-term prognosis was influenced by the presence or absence of a high number of these six risk factors.     

Intracortical excitability in patients with relapsing–remitting and secondary progressive multiple sclerosis

We designed this study to investigate possible correlations between variables measuring primary motor cortex excitability detected by single and paired-pulse transcranial magnetic stimulation (TMS) and the severity of clinical manifestations in patients with multiple sclerosis (MS). Thirty patients with MS in remission, 16 with relapsing–remitting (RR), 14 with secondary progressive disease (SP) and 17 healthy subjects participated in the study. In each subject, the central motor conduction time (CMCT) was calculated, and single-pulse and paired-pulse TMS at 3 and 10 ms interstimulus intervals was delivered over the primary motor cortex of the dominant hemisphere to measure the amplitude of motor-evoked potentials (MEPs), motor threshold (MTh), intracortical inhibition (ICI) and facilitation (ICF). Correlations were determined between the patients’ TMS findings and magnetic resonance imaging (MRI) (lesion load) and clinical features (expanded disability status scale, EDSS score). EDSS scores were significantly higher in SPMS than in RRMS patients. The MTh was significantly higher, and the MEP was significantly smaller in SPMS patients than in RRMS patients and control subjects. All patients had longer CMCTs than healthy subjects. In all patients, paired-pulse TMS elicited an inhibited test MEP at the 3-ms ISI and a facilitated test MEP at the 10 ms ISI. Post hoc analysis showed that ICI was significantly lower in SPMS patients than in those with RRMS and healthy subjects. EDSS scores correlated significantly with TMS measures (MEP, ICI, CMCT and MTh), but not with MRI lesion load. It was found that intracortical excitability as measured with TMS differs according to the clinical course of MS; it remains normal in patients with low EDSS scores and is altered in patients with high EDSS scores.     

Cross-cultural adaptation and validation of multiple sclerosis quality of life questionnaire (MSQOL-54) in a Turkish multiple sclerosis sample

OBJECTIVE: Multiple sclerosis (MS) is a chronic progressive disease with multiple neurological impairments. The disease can also dramatically affect the health-related quality of life of patients. The objective of this study was to investigate the validation of the translated and cross-culturally adapted MSQOL-54 in 183 Turkish MS patients. METHODS: 183 adults classified as having definite MS patients were enrolled into the study. Patients were classified into four severity groups according to the expanded disability status scale (EDSS); group I (EDSS 0-4), group II (EDSS 4.5-5.5), group III (EDSS 6-6.5) and group IV (EDSS 7-8). MSQOL-54 questionnaire were translated and culturally adapted into Turkish. Associations between age, gender, disease duration, EDSS score, marital status, education and health insurance and the MSQOL-54 physical and mental health composite scores were determined. RESULTS: The mean age of the 183 patients (138 female and 45 male) was 39+/-10 years. The questionnaire was well accepted but small cultural adaptations were required. EDSS scores showed significant associations with the MSQOL-54 physical and mental health composite scores. From the different EDSS groups only, the group I (EDSS 0-4) score was significantly associated with the physical health composite as well as the disease duration showed significant correlation with the physical and mental composite scores. None of the other EDSS groups and the other parameters showed correlation with physical health composite or mental health composite. CONCLUSION: Assessment of quality of life of MS patients in addition to disease severity and disability level is important, because it provides unique information that is important to patients and to clinicians. A translation of an existing MS-targeted HRQOL measure from US English into Turkish was easily administered and well accepted in a Turkish MS sample.     

Sensory evoked potentials to predict short-term progression of disability in multiple sclerosis

To devise a multivariate parametric model for short-term prediction of disability using the Expanded Disability Status Scale (EDSS) and multimodal sensory EP (mEP). A total of 221 multiple sclerosis (MS) patients who underwent repeated mEP and EDSS assessments at variable time intervals over a 20-year period were retrospectively analyzed. Published criteria were used to compute a cumulative score (mEPS) of abnormalities for each of 908 individual tests. Data of a statistically balanced sample of 58 patients were fed to a parametrical regression analysis using time-lagged EDSS and mEPS along with other clinical variables to estimate future EDSS scores at 1 year. Whole sample cross-sectional mEPS were moderately correlated with EDSS, whereas longitudinal mEPS were not. Using the regression model, lagged mEPS and lagged EDSS along with clinical variables provided better future EDSS estimates. The R (2) measure of fit was significant and 72% of EDSS estimates showed an error value of ±0.5. A parametrical regression model combining EDSS and mEPS accurately predicts short-term disability in MS patients and could be used to optimize decisions concerning treatment.     

Efficacy of natalizumab in multiple sclerosis patients with high disease activity: a Danish nationwide study

Introduction:  Previous studies of natalizumab (Tysabri®) in relapsing multiple sclerosis (MS) patients have included patients with moderate disease activity. We studied a patient population with high disease activity.
Patients and Methods:  We analyzed data from 234 consecutive, natalizumab-treated patients, followed for at least 3 months. Three groups of patients were eligible for natalizumab therapy: patients with two or more documented relapses or sustained increase of 2 EDSS points on disease modifying therapy (DMT) in the previous year; patients switching from mitoxantrone; and patients with very active MS as de novo therapy.
Results:  During a median observation time of 11.3 months (range 3.0–21.5) the annualized relapse rate decreased to 0.68 from a pre-treatment rate of 2.53 (73% reduction). We assessed the annualized relapse rate in three subgroups: (i) 0.83 in 14 (6.0%) de novo treated patients; (ii) 0.71 in 175 (74.8%) patients with ≥2 relapses or sustained increase in EDSS of ≥2 points on a first-line DMT; and (iii) 0.56 in 45 (19.2%) patients switching from mitoxantrone. Nine anaphylactoid reactions, two severe, were reported. Out of 215 patients 7 (3%) were persistently positive for antibodies to natalizumab.
Conclusions:  Tysabri appears to be effective in MS patients with high disease activity, but the relapse rate was higher than in the pivotal study after the first treatment year. This is likely to reflect differences in disease activity before the initiation of natalizumab treatment.     

New natural history of interferon-beta-treated relapsing multiple sclerosis

OBJECTIVE: To investigate the impact of interferon-beta (IFNbeta) on disease progression in relapsing-remitting multiple sclerosis patients. METHODS: A cohort of 1,504 relapsing-remitting multiple sclerosis (1,103 IFNbeta-treated and 401 untreated) patients was followed for up to 7 years. Cox proportional hazards regression adjusted for propensity score inverse weighting was used to assess the differences between the two groups for three different clinical end points: secondary progression (SP) and irreversible Expanded Disability Status Scale (EDSS) scores 4 and 6. Times from first visit and from date of birth were used as survival time variables. RESULTS: The IFNbeta-treated group showed a highly significant reduction in the incidence of SP (hazard ratio [HR], 0.38, 95% confidence interval [CI], 0.24-0.58 for time from 1st visit; HR, 0.36, 95% CI, 0.23-0.56 for time from date of birth; p < 0.0001), EDSS score of 4 (HR, 0.70, 95% CI, 0.53-0.94 for time from first visit; HR, 0.69, 95% CI, 0.52-0.93 for time from date of birth; p < 0.02), and EDSS score of 6 (HR, 0.60, 95% CI, 0.38-0.95 for time from first visit; HR, 0.54, 95% CI, 0.34-0.86 for time from date of birth; p < or = 0.03) when compared with untreated patients. SP and EDSS scores of 4 and 6 were reached with significant delays estimated by times from first visit (3.8, 1.7, and 2.2 years) and from date of birth (8.7, 4.6, and 11.7 years) in favor of treated patients. Sensitivity analysis confirmed findings. INTERPRETATION: IFN-beta slows progression in relapsing-remitting multiple sclerosis patients.     

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.     

Early abnormalities of evoked potentials and future disability in patients with multiple sclerosis

Evoked potentials (EP) have a role in making the diagnosis of multiple sclerosis (MS) but their implication for predicting the future disease course in MS is under debate. EP data of 94 MS patients examined at first presentation, and after five and ten years were retrospectively analysed. Patients were divided into two groups in relation to the prior duration of disease at the time point of first examination: group 1 patients (n=44) were first examined within two years after disease onset, and group 2 patients (n=50) at later time points. As primary measures sum scores were calculated for abnormalities of single and combined EP (visual (VEP), somatosensory (SEP), magnetic motor evoked potentials (MEP)). In patients examined early after disease onset (group 1), a significant predictive value for abnormal EP was found with MEP and SEP sum scores at first presentation correlating significantly with Expanded Disability Status Scale (EDSS) values after five years, while the VEP sum score was not. The cumulative number of abnormal MEP, SEP and VEP results also indicated higher degrees of disability (EDSS > or = 3.5) after five years. Combined pathological SEP and MEP findings at first presentation best predicted clinical disability (EDSS > or = 3.5) after five years (odds ratio 11.0). EP data and EDSS at first presentation were not significantly linked suggesting that EP abnormalities at least in part represented clinically silent lesions not mirrored by EDSS. For patients in later disease phases (group 2), no significant associations between EP data at first presentation and EDSS at five and ten years were detected. Together with clinical findings and MR imaging, combined EP data may help to identify patients at high risk of long-term clinical deterioration and guide decisions as to immunomodulatory treatment.     

Depression, disability and cognitive impairment in multiple sclerosis: a cross sectional Italian study

The disability, cognitive impairment, fatigue and depression are interacting features in multiple sclerosis (MS), whose relation is still unclear. The objective of this study was to evaluate in a sample of MS patients, the frequency of depressive symptoms, its predicting factors and relation with cognitive impairment, fatigue and disability. 255 consecutive MS patients and 166 healthy subjects were assessed for the presence of depressive symptoms with the Beck Depression Inventory-Fast Screen (BDI-FS). Patients with BDI-FS ≥4 were further investigated for the presence of neuropsychological impairment. Depressive symptoms were significantly more frequent and severe in patients than in controls. EDSS score was the only predicting factor of depression (3.5 = threshold EDSS score for depressive symptoms) in patients, whereas neuropsychological impairment was not correlated with BDI-FS and fatigue was found to be significantly correlated with attention, executive function and memory test scores, as well as with BDI-FS score in patients.     

Health-related quality of life and depression in an Italian sample of multiple sclerosis patients

Only few publications have been reported on Health-related Quality of Life (HRQoL) in patients with multiple sclerosis (MS). EDSS is the most common outcome measure for either impairment or disability of MS, but it is not able to catch other aspects of MS impact on HRQoL.The authors performed a cross-sectional study on the group of all patients with MS who were diagnosed at least 4 years before 1998 in Catania (South Italy). One hundred and eighty patients out of 308 were enrolled in the study. SF-36 was used to catch the HRQoL of MS patients. EDSS, Beck Depression Inventory (BDI) and time since diagnosis were investigated as variables affecting the HRQoL of MS patients.The patients showed significant lower mean scores for all SF-36 health dimensions compared with sex- and age-adjusted scores in a general healthy Italian population (p<0.001). EDSS scores correlated only with physical functioning (r=-0.76 p<0.001). As expected, the more severe was the disease, the longer its duration and the lower the patients' skillness on HRQoL. BDI showed high partial correlations with all SF-36 health domains with r=-0.38 to -0.65 (p<0.001).This study showed that SF-36 is able to assess the HRQoL of MS patients. Depression strongly influenced the HRQoL of MS patients. EDSS and time since diagnosis also affected the HRQoL of MS patients. Our results are comparable with other European studies.     

Exploring cognitive reserve in multiple sclerosis: New findings from a cross-sectional study

Introduction: The cognitive reserve (CR) hypothesis attempts to explain the discrepancy between brain damage and clinical manifestations in neurodegenerative diseases. Recently the concept of CR was applied to the multiple sclerosis (MS) model. Our aim is to investigate the impact of demographic and clinical variables on cognitive outcome in MS patients. Method: A total of 72 MS patients were assessed by Rao’s Brief Repeatable Battery of Neuropsychological Tests (BRB-N), Cognitive Reserve Index Questionnaire (CRIq), and high field magnetic resonance examination. We performed a multivariate linear regression analysis, including each cognitive test scores as dependent variables and CRI together with age, normalized brain volume (NBV), normalized cortical volume (NCV), expanded disability severity scale (EDSS) score, and disease duration as independent variables. Moreover, we assessed whether one of the CRI subscores (CRI–Education, CRI–WorkingActivity, CRI–LeisureTime) predicted cognitive performance more than the other. Finally, to assess the CR hypothesis in our sample, we conducted the same analyses including the interaction term CRI × NCV. Results: From the multiple regression analysis, it emerged that the CRI total score influenced sustained attention, concentration, information processing speed, and verbal learning. Among the three CRI subscores, CRI–Education and CRI–WorkingActivity had the most influence. Age and EDSS score were the other significant predictors. We did not find evidence for a moderation effect of CR on negative influence of atrophy on cognitive status. Conclusions: This study focused on the contribution of CR to predict neuropsychological outcome in MS. We used a new standardized questionnaire to provide a global index including three main source of CR: education, working activity, and leisure time activities. Our preliminary findings suggest that the CR is an important predictor of better performance on cognitive tests in MS patients. However, at this stage of the study, we are unable to confirm the CR hypothesis.     

Multiple Sclerosis Impact Scale (MSIS-29): relation to established measures of impairment and disability

OBJECTIVE: To validate the newly developed Multiple Sclerosis Impact Scale (MSIS-29) in a large, well characterized, independent group of MS patients by investigating the relation between the MSIS-29 and the Guy's Neurological Disability Scale (GNDS), the Expanded Disability Status Scale (EDSS) and the MS Functional Composite (MSFC). METHODS: Two hundred MS patients were recruited at our outpatient department. At the same visit GNDS, EDSS, MSFC and MSIS-29 were assessed. Data obtained from GNDS, EDSS and MSFC assessment were compared to both physical and psychological impact scores of the MSIS-29. In addition the contribution of GNDS subcategories, EDSS functional systems and MSFC components to the physical and psychological impact scores of the MSIS-29 was studied. RESULTS: Median scores were 37.5 for the physical and 22.2 for the psychological impact score of the MSIS-29, 13.0 for GNDS and 4.0 for EDSS. Mean MSFC was 0.07. The physical impact score showed good correlations with both GNDS (0.79) and EDSS (0.68) and a moderate correlation with the MSFC (-0.53). The psychological impact score showed weak correlations with EDSS (0.22) and MSFC (-0.30) and a moderately strong correlation with the GNDS (0.58). In 50 (25%) patients, scores on physical and psychological impact scales diverted, i.e., a relative high score on one scale combined with a relative low score on the other scale. This was related to the clinical disease course. CONCLUSION: Our study supports the use of the MSIS-29 as a measure for the assessment of physical impact of MS on normal daily life. In addition, our data provides a deeper understanding of the factors that determine both physical and psychological disease impact. Discrepancies between the latter two aspects deserve further attention.     

Association of subjective anxiety, depression, and sleep disturbance with quality-of-life ratings in adults with epilepsy

Purpose :  To determine the relative contributions of subjective anxiety, depression, sleep disturbance, and seizure-related variables to quality-of-life scores in adults with epilepsy, and the interrelationships among these factors.
Methods :  Consecutive adult patients with epilepsy attending neurology outpatient clinics were recruited. Patients completed the following scales: Hospital Anxiety and Depression Scale (HADS), Hamilton Anxiety Rating Scale, Medical Outcomes Study (MOS) Sleep Scale, Epworth Sleepiness Scale, and Quality of Life in Epilepsy Inventory-31 (QOLIE-31). Univariate and multivariate linear regression models were used to identify variables associated with QOLIE-31 overall score. Path analysis model was constructed to test for interrelations between the variables.
Results :  Two hundred forty-seven patients completed the questionnaires. By multivariate analysis, in order of degree of contribution, HADS anxiety subscale score, MOS Sleep Scale Sleep Problems Index score, HADS depression subscale score, number of current antiepileptic drugs used, and seizure freedom in the past 4 weeks, significantly correlated with QOLIE-31 overall score, accounting for 65.2% of the variance. Complex interrelationships were present between these factors. A general linear model to predict QOLIE-31 overall score in the presence of these factors was constructed.
Conclusion :  Subjective anxiety, depression, and sleep disturbance exerted greater effect than short-term seizure control on quality of life scores of patients with epilepsy. These factors should be considered simultaneously when evaluating effects of treatment on quality of life.     

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.