Higher Expanded Disability Status Scale Scores Research Articles

Intrathecal IgM synthesis in pediatric MS is not a negative prognostic marker of disease progression: quantitative versus qualitative IgM analysis

Background: Intrathecal IgM synthesis is reported to be associated with a worse prognosis in adults with multiple sclerosis (MS). Objective: To study the predictive value of intrathecal IgM synthesis for the clinical course of pediatric MS. Methods: Seventy children with onset of MS before the age of 16 years and followed for a median period of 10.4 years (range: 0.4–22.8 years) were studied. The two subgroups with (n = 44) or without (n = 26) intrathecal IgM synthesis were distinguished by a new, very sensitive, evaluation of quantitative analysis in cerebrospinal fluid (CSF)/serum quotient diagrams (Reibergrams). The clinical course and EDSS (Expanded Disability Status Scale) scores at five and ten years were compared with IgM frequencies between both groups with a new statistics program for CSF data. Results: The cohort of children without intrathecal IgM production had higher numbers of attacks in the first two years and shorter time intervals between first and second attack, although this was not statistically significant (p = 0.04, p = 0.15 respectively). In addition there was also a trend for girls without intrathecal IgM synthesis to have a higher EDSS score after 10 years compared with the group with IgM synthesis. Conclusion: Intrathecal IgM synthesis is not associated with a more rapid progression of disability in pediatric MS. Reevaluation of data from previous reports about the negative predictive value of intrathecal IgM synthesis in adult MS with a CSF statistics tool show that the apparent contradiction is due to a methodological bias in the qualitative detection of ‘oligoclonal’ IgM or linear IgM index.

Diffusion Tensor Imaging Abnormalities in Cognitively Impaired Multiple Sclerosis Patients

Cognitive impairment can add to the burden of disease in patients with multiple sclerosis (MS). The aim of this study was to assess the relative importance of diffusion tensor imaging (DTI) indices derived from normal appearing white matter (NAWM) and grey matter (NAGM) in determining cognitive dysfunction in MS patients. Sixty two MS patients [51 female, mean age = 41 (sd = 9.6) years, median expanded disability status scale (EDSS) = 2.5] meeting modified McDonald criteria for MS underwent neuropsychological testing using the Neuropsychological Screening Battery for MS (NSBMS) and magnetic resonance imaging (MRI, 1.5T GE) that included DTI sequences. Total T1 hypointense and T2 hyperintense lesion volumes were obtained using semi-automated software. Lesion volumes were subtracted from whole-brain parenchyma to obtain measures of NAWM and NAGM. Fractional anisotropy (FA) of NAWM and mean diffusivity (MD) of NAGM were obtained. Cognitive impairment was present in 11 patients (18%). These patients had higher EDSS scores, were less educated, and were more likely to have secondary progressive MS. They also had higher hypointense (p = 0.001) and hyperintense (p = 0.004) lesion volumes, greater NAWM atrophy (p = 0.007), lower FA of total NAWM (p = 0.003), and higher MD of total NAGM (p = 0.015). Using a logistic regression analysis, and after controlling for demographic and disease-related differences between groups, FA of NAWM emerged as a significant predictor of cognitive impairment adding to the variance derived from lesion and atrophy data. This study underlies the important role of normal-appearing brain tissue in the pathogenesis of MS-related cognitive impairment.

Effects of Antimicrobial Prophylaxis on Asymptomatic Bacteriuria and Predictors of Failure in Patients with Multiple Sclerosis

We studied the effects of antimicrobial prophylaxis and possible predictors of failure in multiple sclerosis patients with bacteriuria and bladder dysfunction. Patients were categorized into 3 groups, according to post-voided residual urine volume (PVR): patients with indications for self intermittent catheterization (SIC) who elected (Group A, n=39) or not (Group b, n=53) to use SIC and patients with no indication for SIC (Group C, n=75). In group A, 90% of patients developed bacteriuria after SIC. Rates of bacteriuria in groups b and C were significantly lower (34% and 24%, respectively, all p<0.001). prophylaxis failed in 31% and 22% of patients in groups A and b, respectively whereas all group C patients responded to prophylaxis. Symptomatic urinary tract infection was observed only in 14% of group A patients. Significant predictors of prophylaxis failure were an expanded disability status scale (EDSS) score ≥6 (p≤0.05), a high PVR (p≤0.075) and resistance to prophylaxis regimen (p≤0.007). SIC did not have a significant association with prophylaxis failure. In multivariate analysis only a higher EDSS score (≥6) predicted prophylaxis failure (p=0.019).

Driving Behaviors Among Community-Dwelling Persons With Multiple Sclerosis

Schultheis MT, Weisser V, Manning K, Blasco A, Ang J. Driving behaviors among community-dwelling persons with multiple sclerosis. Objective The current study examined driver behaviors and patterns among drivers with multiple sclerosis (MS) as a function of disease severity and in comparison to drivers without MS. Design Between-group comparisons of participants with and without MS and cohorts of MS groups at varying levels of severity. Setting All data were collected in an outpatient research setting. Participants Community-dwelling persons (n=66) with clinically definite MS who were active drivers and healthy controls (n=30) were included. Interventions Not applicable. Main Outcome Measures Driving characteristics' measures included (1) driving frequency defined in days and miles driven per week, (2) self-reports of voluntarily limited driving behaviors, (3) changes in driving since MS diagnosis, and (4) self-rating as a driver. Driving performance was also assessed by using pass/borderline performance on a clinical behind-the-wheel evaluation. Results Mann-Whitney U tests showed a significant difference in driving frequency ( P=.021) with MS participants reporting they drove fewer days per week than healthy control group. This was also seen between cohorts of MS drivers ( P=.014), with high Expanded Disability Status Scale (EDSS) participants driving less frequently than the low EDSS group. Descriptive observations suggested that participants with moderate EDSS scores drove less and engaged in more self-limiting behaviors. Chi-square tests showed that participants with high EDSS scores were more likely to report changing their driving behavior after diagnosis ( P=.01) and were more likely to not pass the behind-the-wheel evaluation ( P<.001). Conclusions The current findings suggest that as disease severity progresses, differences in frequency of driving (days per week) and the use of self-limiting driving behaviors may vary. Furthermore, the findings also raise questions regarding the overall sensitivity of the most commonly used clinical driving assessment method (the behind-the-wheel evaluation) to accurately capture driving capacity in the milder stages of the disease process. The results indicate the need to consider issues related to driving as MS severity progresses, and, given the progressive nature of MS and the concerns of the validity of the most common clinical driving assessment measures (the behind-the-wheel evaluation), repeated assessment of driving ability may be the most effective approach for identifying driving difficulties among persons with MS.

Kallikreins are associated with secondary progressive multiple sclerosis and promote neurodegeneration

Tissue kallikrein KLK1 and the kallikrein-related peptidases KLK2-15 are a subfamily of serine proteases that have defined or proposed roles in a range of central nervous system (CNS) and non-CNS pathologies. To further understand their potential activity in multiple sclerosis (MS), serum levels of KLK1, 6, 7, 8 and 10 were determined in 35 MS patients and 62 controls by quantitative fluorometric ELISA. Serum levels were then correlated with Expanded Disability Status Scale (EDSS) scores determined at the time of serological sampling or at last clinical follow-up. Serum levels of KLK1 and KLK6 were elevated in MS patients (p<or=0.027), with highest levels associated with secondary progressive disease. Elevated KLK1 correlated with higher EDSS scores at the time of serum draw and KLK6 with future EDSS worsening in relapsing remitting patients (p<or=0.007). Supporting the concept that KLK1 and KLK6 promote degenerative events associated with progressive MS, exposure of murine cortical neurons to either kallikrein promoted rapid neurite retraction and neuron loss. These novel findings suggest that KLK1 and KLK6 may serve as serological markers of progressive MS and contribute directly to the development of neurological disability by promoting axonal injury and neuron cell death.

How similar are commonly combined criteria for EDSS progression in multiple sclerosis?

Introduction Measuring disease progression is an important aspect of multiple sclerosis (MS) clinical trials. Commonly applied disability endpoints include time to clinically meaningful Expanded Disability Status Scale (EDSS) change, or the number of patients in whom such a change has occurred. Typically, clinically meaningful EDSS change has been defined as a change of 1.0 point on Kurtzke’s EDSS in patients with an entry EDSS score of 5.5 or lower, or 0.5 point in patients with a higher EDSS score. Our goal was to evaluate whether these changes can be considered as similar. Therefore, we compared EDSS changes to corresponding changes in the Guy’s Neurological Disability Scale (GNDS), which is a measure of patient perceived disability, and the Multiple Sclerosis Functional Composite (MSFC), which is an examination-based quantitative scoring of neurological impairment. Methods From a large longitudinal database, we selected two groups of patients with a clinically meaningful change in EDSS score according to the usual criteria: patients with EDSS change]/1.0 for baseline EDSS 5/5.5 and patients with EDSS change]/0.5 for baseline EDSS]/6.0. We compared changes in GNDS sum score and in MSFC score between both groups. Results In the group with baseline EDSS]/6.0, GNDS and MSFC changes were higher than in patients with baseline EDSS 5/5.5. The difference in change was 1.00 (95% confidence interval (CI): / 0.35 to 2.36) for the GNDS and 0.412 (95% CI: 0.300-0.525) for the MSFC. Conclusion Our results indicate that a 0.5 point EDSS change in patients with baseline EDSS / 6.0 cannot be considered equal to a 1.0 point change in patients with baseline EDSS 5/5.5.

Can the Expanded Disability Status Scale be assessed by telephone?

Information from patients who are unable to continue their visits to a study centre may be of major importance for the interpretation of results in multiple sclerosis (MS) clinical trials. To validate a questionnaire based on the Expanded Disability Status Scale (EDSS), patients in five different European centres were assessed independently by pairs of trained EDSS raters, first by telephone interview and a few days later by standardized neurological examination. Seventy women and 40 men with an average age of 43.7 years (range 19-74 years) were included in the study. Mean EDSS score at the last visit was 4.5 (0-9). EDSS assessment by telephone was highly correlated with the EDSS determined by physical examination (Pearson's correlation coefficient = 0.95). An intraclass correlation coefficient (ICC) of 94.8% was found for the total sample; 77.6% and 86%, respectively, for patients with EDSS < 4.5 (n = 46) and > 4.5 (n = 64). Kappa values for full agreement were 0.48; for variation by +0.5 steps and +1.0 steps, 0.79 and 0.90, respectively. Best agreement could be found in higher EDSS scores, where assessment by telephone interview might be needed most. The telephone questionnaire is a valid tool to assess EDSS score in cases where the patient is unable to continue visiting a study centre or in long-term follow-up of trial participants.

Impact of Multiple Sclerosis on Family and Employment: A Retrospective Study in the Aegean District of Turkey

Abstract We investigated many of the effects of multiple sclerosis (MS) on patients in the Aegean District of Turkey who have had the disease for longer than one year to establish their social and occupational needs. Questions covered income, marital status, employment status of patient and spouse, housing, employment status of children, special care needs, and what changes had occurred in any of the preceding areas due to the illness. Our survey questionnaire yielded responses from 246 MS patients (ages 16–65; 87 men, 159 women) from the outpatient departments of six centers in Izmir, Turkey. The survey was conducted from March 2, 1998, to March 5, 1999. Survey results were tabulated and analyzed statistically for correlations between factors and were similar to other reports from western countries. Men reported reduced income and higher unemployment than women, many of whom were housewives. First-degree relatives carried the burden of caregiving. Disease duration and higher Expanded Disability Status Scale (EDSS) scores were strongly correlated with changes in employment, marital status, and housing. Higher EDSS scores had a negative impact on the spouse's work and the patient's need for care. Among disease types, secondary progressive MS (SPMS) also negatively affected the family structure. The disease had little effect on children's employment status.

Quality of life and its relationship to brain lesions and atrophy on magnetic resonance images in 60 patients with multiple sclerosis.

Disease-modifying multiple sclerosis (MS) therapeutic trials continue to rely on physical disability as the main clinical outcome measure, while the impact of treatment on quality of life (QOL) is poorly understood. Weak correlations exist between physical disability and the disease burden as shown using conventional brain magnetic resonance imaging (MRI), indicating poor sensitivities of these measures alone in defining the clinical course of MS. To investigate the impact of MS on QOL; to determine whether impaired QOL in patients with MS was related to any regional brain abnormalities assessed using conventional MRI sequences; and to determine if the severity of MS as assessed by the Expanded Disability Status Scale (EDSS) and clinical course was associated with worsening QOL. Prospective, cross-sectional study of 60 consecutive patients with MS treated in a community-based, university-affiliated MS clinic. Assessments of QOL using the Multiple Sclerosis Quality of Life-54 Instrument were correlated with the scores of the EDSS, clinical course, and findings on brain MRI. Quality of life was significantly impaired in patients with MS and was worse in patients with secondary-progressive MS compared with those with relapsing-remitting MS. Brain MRI lesions and atrophy were associated with impaired QOL with respect to sexual dysfunction, overall mental health, and limitations due to physical and emotional dysfunction. Correlations between MRI results and QOL assessments were much stronger for hypointense lesions and atrophy on T1-weighted images than for hyperintense lesions on T2-weighted images and were insignificant for lesions on contrast-enhanced images. Higher EDSS scores were associated with impairments in most physical and mental health QOL scales but were weakly correlated with cognitive and sexual dysfunction. In patients with MS, QOL is impaired and is associated with increasing neurologic disability. Quality of life assessments are related in part to brain lesions and atrophy shown on MRI. Assessments of QOL provide unique information not readily evaluated by EDSS and may be useful as secondary clinical outcome measures. Arch Neurol. 2000;57:1485-1491

Impacto de la fatiga en la esclerosis múltiple: estudio de una serie de base poblacional en Valladolid

Fatigue is one of the commonest findings in multiple sclerosis (MS) although it has scarcely been investigated as an independent symptom. To evaluate the effect of fatigue in a population based series of patients with MS and to analyze its relation to other clinical variables. A descriptive, transverse study based on a geographically defined population. Fatigue was measured using the Krupp scale in 48 patients with definite clinical MS. We analyzed the relation between the degree of fatigue and sex, age of onset, age at the time of the study, type of evolution, index of progression of disability, duration of illness and degree of impairment according to the Expanded Disability Status Scale (EDSS) and neurological functional systems. 64.6% of the patients had a significant degree of fatigue. Of these, 90% considered fatigue to be one of the three most disabling symptoms of their illness. There was no difference between men and women in their perception of fatigue. The patients with progressive illness, of greater age and those with higher EDSS scores had more fatigue. This aspect was not affected by age of onset, duration of illness nor index of progression. Fatigue should be evaluated as an independent symptom of MS. Evaluation using specific scales may contribute to better understanding of the physiopathology and investigation of more effective treatment.

Inter- and intrarater scoring agreement using grades 1.0 to 3.5 of the Kurtzke Expanded Disability Status Scale (EDSS). Multiple Sclerosis Collaborative Research Group.

We determined inter- and intrarater Kurtzke Expanded Disability Status Scale (EDSS) scoring agreement for four trained examining physicians who evaluated 10 clinically stable multiple sclerosis patients. These patients had previously been determined to have EDSS scores of 1.0 to 3.5 and were scheduled to participate in a funded clinical trial of intramuscular recombinant interferon-beta. Intrarater reliability was greater than interrater reliability for scoring the EDSS and all of its component functional systems scores (FSS). Specifically, individual examiners were able to reproduce three serial examination scores on the same patient on the same day (intrarater agreement) within 1.0 EDSS or 2.0 individual FSS points. Reproducible scoring across examiners (interrater agreement), however, could only be accomplished within 1.5 EDSS or 3.0 individual FSS points. Additionally, the interrater scoring variability in our patients is greater than that previously reported for patients with higher EDSS scores. We conclude that clinical trials that employ the EDSS as an outcome measure of treatment efficacy should include inter- and intrarater agreement data for all examining physicians. Most importantly, studies using a single examining physician to evaluate individual patients throughout the course of a clinical trial will require less change in the EDSS to reliably measure disease activity than will studies using more than one examining physician to evaluate individual patients throughout the trial.

Car allowance for consultants

<h3>Objective</h3> To assess the role of CSF chitinase 3-like-1 (CHI3L1), chitinase 3-like-2 (CHI3L2), and neurofilament light chain (NfL) in predicting the course of primary progressive MS (PPMS). <h3>Methods</h3> We analyzed CSF CHI3L1, CHI3L2, and NfL levels in 25 patients with PPMS with disease duration ≤10 years and no disease-modifying therapy for ≥6 months from the prospective Understanding Primary Progressive Multiple Sclerosis cohort study. CSF samples taken at disease diagnosis were analyzed using commercial ELISAs and following the manufacturer9s instructions. Data on Expanded Disability Status Scale (EDSS) scores, disability progression, and cognitive function according to the Brief Repeatable Neuropsychological Battery were also assessed throughout the 1-year study follow-up. <h3>Results</h3> Increasing CHI3L1 levels correlated with higher EDSS scores at baseline (ρ = 0.490, 95% CI 0.118–0.742, <i>p</i> = 0.013) and month 12 (ρ = 0.455, 95% CI 0.063–0.725, <i>p</i> = 0.026) and tended to be associated with a higher risk of disability progression according to EDSS scores (OR = 1.008, 95% CI 0.999–1.017, <i>p</i> = 0.089). Increasing CHI3L2 levels also tended to correlate with lower baseline EDSS scores (ρ = −0.366, 95% CI -0.676–0.054, <i>p</i> = 0.086). There was no correlation with regard to NfL levels. <h3>Conclusions</h3> This analysis supports the association between CSF CHI3L1 levels and neurologic disability according to EDSS scores in patients with PPMS. Other chitinase-like proteins such as CHI3L2 may also be involved. <h3>Classification of evidence</h3> This study provides Class II evidence that CSF CHI3L1 is associated with neurologic disability in patients with PPMS.