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.     

Multimodal evoked potentials measure and predict disability progression in early relapsing-remitting multiple sclerosis

In 37 patients with early relapsing-remitting multiple sclerosis (RRMS), a multimodal EP score (mEPS) and clinical scores (Expanded Disability Status Scale (EDSS) and multiple sclerosis functional composite (MSFC)) were obtained prospectively over 24 months. Changes in mEPS correlated with changes in EDSS (Spearman's rho = 0.69, p < 0.0001) and MSFC (rho = -0.41, p < 0.02). Patients with relevant EDSS progression (n = 7) showed stronger mEPS deterioration than clinically stable patients (10.8 +/- 3.2 versus 1.3 +/- 0.8, p < 0.005). Baseline mEPS was not significantly correlated with baseline EDSS but with EDSS after 24 months (rho = 0.39, p < 0.02). The data suggest that serial mEPS measure and moderately predict clinically relevant disease activity in the therapeutically most relevant early stage of RRMS.     

Long-term clinical outcome of primary progressive MS: predictive value of clinical and MRI data

The authors sought to identify clinical and MRI predictors of outcome in primary progressive multiple sclerosis (PPMS). Clinical and MRI assessments were performed at baseline and 2 and 5 years (clinical only). At baseline, disease duration, expanded disability status scale (EDSS) and brain volume predicted outcome. Adding short-term change variables, baseline EDSS, changes in T2* lesion load and cord area, and number of new lesions were predictive. Clinical and MRI variables predict long-term outcome in PPMS.     

Clinical and conventional MRI predictors of disability and brain atrophy accumulation in RRMS

To assess the value of clinical and MRI variables in predicting short-term brain atrophy accumulation and clinical evolution in a large cohort of patients with RRMS, we studied a cohort of 548 patients, previously enrolled as a placebo arm of a 14-month, double-blind trial of oral glatiramer acetate (GA). A logistic regression model with EDSS progression as the dependent variable was built to assess baseline clinical and MRI variables associated with clinical worsening during follow-up. In 466 patients with complete central brain atrophy assessment, another linear regression model with percentage central brain volume change (PCBVC) as the dependent variable was built to assess baseline clinical and MRI variables associated with atrophy development. A total of 80 patients (15 %) had EDSS progression over the follow-up period. Factors independently predicting the probability to have a clinical progression were lower EDSS (OR = 0.78, 95 % CI = 0.62–0.97 p = 0.02) and higher T2 LL (OR = 1.022, 95 % CI = 1.006–1.038, p = 0.007) at baseline. In the 466 patients with atrophy assessment, PCBVC declined, on average, by –2.0 % (SD = 2.8) (p < 0.001) over the follow-up. The multivariate PCBVC analysis revealed that the PCBVC decrease was independently correlated with higher EDSS (p = 0.03) and T2 LL (p = 0.005) at baseline. The squared correlation coefficients of the composite scores made up of EDSS and T2 LL considered together were able to explain only 3 % of the variance in disability progression and only 4 % of the variance of PCBVC. In RRMS patients, clinical and conventional MRI findings at baseline only modestly predict shortterm accumulation of brain atrophy and disability. These data confirm the need to develop clinical and MRI measures more sensitive towards the more disabling aspects of the disease.     

Self-rated physical health predicts change in disability in multiple sclerosis

OBJECTIVE: To examine whether self-rated physical health, as measured by the Physical Functioning Scale (PF) and the Role-physical Scale (RF) of the SF-36 Health Survey, could predict change in disability measured by the Expanded Disability Status Scale (EDSS) in patients with multiple sclerosis (MS) over a follow-up period of 3 years. METHODS: A group of 156 clinically definite MS patients (Poser criteria), who had never been treated with disease-modifying therapies, were recruited consecutively from an outpatient clinic setting at the Institute of Neurology, Belgrade. The self-rated physical health was measured by using PF and RF of the SF-36. RESULTS: At follow-up, 33 out of 156 patients (21%) had dropped out. The mean EDSS score had increased from 3.7 to 4.5. Multiple regression analyses using change in EDSS as the dependent variable and baseline scores of EDSS and RF as independent variables showed a significant effect for RF (standardized beta= -0.21). A similar but non-significant effect was found for PF. Dichotomizing change in disability according to clinically meaningful deterioration and using logistic regression, an odds ratio of 1.27 (95% confidence interval 1.01-1.62) was found for the smallest unit of change in the self-rated scale. This means that patients who rated their own physical health as poor had a higher increase in disability compared with patients with the same level of disability at baseline who rated their physical health better. CONCLUSIONS: MS patients' perception of their health comprises information predictive for disease development not included in the more objective measure of disability status.     

The multiple sclerosis functional composite: a new clinical outcome measure for multiple sderosis trials

With the advent and widespread use of partially effective disease modifying drug therapies for multiple sderosis (MS), future dinical trials will undoubtedly test experimental interventions against standard therapy, or will test combinations of drugs against standard therapy. In either case, incremental progress in slowing disability progression in future MS dinical trials will require much larger sample sizes, more sensitive outcome measures, or a combination of the two. Because improved dinical outcome methods would likely accelerate progress in MS therapeutics, the National Multiple Sclerosis Society (NMSS) convened an international task force in 1994 to recommend improved clinical outcome measures. As the result of a two-year process of discussion and data analysis, the task force recommended the Multiple Sderosis Functional Composite (MSFC) as a new clinical outcome measure for future MS trials. MSFC consists of timed tests of walking, arm function, and cognitive function, expressed as a single score along a continuous scale. The task force recommended that MSFC be induded in future MS trials, and recommended a series of validation studies. Subsequent studies have provided evidence that MSFC correlates moderately with Expanded Disability Status Scale (EDSS), and that correlation is driven by strong correlations with the ambulatory function component; arm function and cognitive function correlate at lower levels with EDSS. The MSFC correlates better than EDSS with magnetic resonance imaging (MRI) variables, including brain atrophy, and shows significant correlation with patient-reported disease-related quality of life (QOL). MSFC and short-term change in MSFC correlate with future clinical and MRI status, and the strength of the correlations compares favorably with well-known cardiovascular risk factors. The studies in aggregate indicate that MSFC and MSFC change are clinically meaningful, and that MSFC has substantial advantages over alternative clinical outcome measures for MS clinical trials.     

Magnetization transfer magnetic resonance imaging and clinical changes in patients with relapsing-remitting multiple sclerosis

BACKGROUND: Magnetization transfer (MT) magnetic resonance imaging (MRI) can provide in vivo quantitative estimates of microscopic tissue damage in normal-appearing white matter (NAWM) and gray matter (GM) from patients with multiple sclerosis (MS). OBJECTIVE: To determine whether a one-time MT MRI can provide markers of short-term disease evolution in patients with relapsing-remitting MS. DESIGN: Eighteen-month observational study. SETTING: Neuroimaging Research Unit, Scientific Institute and University Ospedale San Raffaele. PATIENTS: Twenty-two patients with untreated relapsing-remitting MS. MAIN OUTCOME MEASURES: Relapse rate; disability according to the Expanded Disability Status Scale (EDSS); dual-echo, 2-dimensional gradient echo with and without a saturation MT pulse and T1-weighted MRIs of the brain; and MT ratio (MTR) histograms for NAWM and GM. RESULTS: During the study period, 13 patients (59%) experienced 25 relapses. The median EDSS score was 1.25 (range, 0-3.5) at study entry and 1.75 (range, 0-3) at study exit. Significant, although moderate, correlations were found between average GM MTR values at baseline and EDSS changes during the study period (r = -0.44; P = .04). A trend was observed for the correlation between NAWM MTR values at baseline and the EDSS changes throughout 18 months (r = -0.42; P = .05). For the relation between EDSS changes and baseline GM MTR, the slope of the regression line was -0.5 (95% confidence interval, -1.0 to 0.0), indicating that a decrease in the baseline GM MTR of 1% predicted an increase in the EDSS score of 0.5 point throughout the 18 months. CONCLUSION: This study indicates that a "snapshot" MT MRI assessment detects subtle brain tissue changes that are associated with short-term disability accumulation in patients with relapsing-remitting MS.     

Multiple sclerosis in Italy: cost-of-illness study

This study estimates the direct costs of multiple sclerosis (MS) in Italy from the perspective of the National Health System. Patients diagnosed with MS for ≥1 year prior to study entry were included in the analysis; neurological disability was assessed using the Expanded Disability Status Scale (EDSS). Cost variables were analyzed according to: MS phenotype, disease course over the previous year and EDSS rating. A total of 510 patients were included in the analysis. Overall costs were significantly higher for relapsing-remitting MS and secondary progressive MS than for primary progressive MS (P < 0.05). Costs were higher for EDSS scores 0.0–3.5 and 4.0–6.0 than for scores > 6.0 (P < 0.05). The extrapolated data gave an estimated annual direct cost of MS per patient of €18,030. In conclusion, relapsing-remitting MS or secondary progressive MS phenotypes and lower estimated EDSS scores appear to be associated with higher costs.     

Cerebrospinal fluid/serum gradient of IgG is associated with disability at acute attacks of neuromyelitis optica

Increased blood-brain barrier (BBB) disruption can be found in patients with neuromyelitis optica (NMO); however, its clinical implication and association with disability at acute attack remains obscure. The purpose of the study was to evaluate the clinical significance of BBB disruption and the subsequent cerebrospinal fluid (CSF)/serum IgG gradient in NMO. Retrospective analysis was made of acute-stage CSF samples from NMO (n = 40) and multiple sclerosis (MS; n = 26) patients. The CSF/serum IgG gradient (QIgG), albumin ratio (Qalb), and IgG index were calculated. Multivariate regression analysis was used to identify clinical and CSF variables associated with disability at acute attacks (extended disability scale score, EDSS) in both groups. The EDSS was significantly associated with the QIgG (p < 0.001), Qalb (p = 0.012), and number of cumulative attacks (p = 0.012) in NMO but not in MS with univariate analysis. Length of spinal cord involvement was also associated with EDSS in NMO (p = 0.030). However, multivariate analysis revealed that the QIgG was only significantly associated with EDSS in NMO (0.580; 95% CI -0.257, 0.961; p = 0.002). The QIgG was also highly associated with the Qalb in NMO (p < 0.001). The QIgG may reflect systemic IgG leakage into the CNS and is strongly associated with disability at acute attacks in NMO, suggesting that BBB disruption can aggravate disease activity by facilitating systemic IgG infiltration into the CNS.     

Anorectal dysfunction in multiple sclerosis

OBJECTIVE: To ascertain the prevalence of anorectal dysfunction (ARD) in patients with multiple sclerosis (MS) and its relationship with MS clinical characteristics. METHODS: Prospective transversal study in 193 patients with MS. All patients fulfilled a protocol that included: demographic variables, clinical characteristics of MS and the presence of ARD and urinary dysfunction (UD). RESULTS: One hundred and ninety-three patients: 66.8% women, an average age of 42.8 (12.1) years; 67.8% of patients had relapsing remitting MS, 21.2% a secondary progressive and 10.9% a primary progressive form. The average duration of MS was 10.7 (9.4) years and the EDSS 2.8 (2.3). ARD was present in 93 patients (48.2%), and UD in 50.2%. ARD associated to UD was present in 35.7% of cases. The univariate study revealed that patients with ARD were older (P <0.001), had greater disability (P <0.0001), longer disease duration (P <0.001) and a greater association with UD (P<0.0001). ARD was more frequent in progressive forms (P<0.0001). The logistic regression analysis showed that female sex (P = 0.015), EDSS (P = 0.002) and UD (P = 0.003) were independent factors related to ARD. CONCLUSION: ARD is a highly prevalent disorder in MS. Female sex, EDSS and UD are independent predictors of ARD development.     

Self-perceived physical functioning and health status among fully ambulatory multiple sclerosis patients

We investigated the self-perceived health status among multiple sclerosis (MS) patients with no or mild disability according to the Expanded Disability Status Scale (EDSS) and the impact of self-rated physical functioning. A sample of fully ambulatory (EDSS ≤ 3.5) consecutive patients with MS was included after screening for major cognitive impairment. The EDSS was used to measure nervous system signs or disability, and the self-rated health status was assessed using the SF-36 Health Survey. The normative SF-36 data for the general population of Italy were used for comparison. The 197 MS patients analyzed (150 women and 47 men) had significantly lower mean SF-36 scores than the general population, except for bodily pain. The scores did not differ significantly by gender. The same analysis performed on a subsample of 105 patients (79 women and 26 men) with minimal disability in one functional system (EDSS ≤ 2.0) yielded similar results. EDSS was weakly correlated with the physical functioning subscale and explained only 2% of the variance in the physical functioning subscale. The regression of the physical functioning subscale on the other seven SF-36 subscales was significantly lower among MS patients than in the general population for all subscales, except for role limitation due to physical health problems and social functioning. Neither disease course nor duration correlated significantly with SF-36 subscales. The SF-36 physical functioning subscale seemed to indicate physical functioning more sensitively than EDSS. These findings should encourage the implementation of specific strategies aimed at improving the quality of the self-perceived health status already in the early disease stage.     

New disposition for pain therapy in Italy,center for headache should be integrated in the network

Multiple sclerosis (MS) patients frequently develop some form of ocular motor dysfunction during the disease. In previous studies, ocular motor abnormalities were found to correlate with clinical disability and with impaired cognitive performance. The objective of this study was to assess the pursuit ocular movement (POM) frequency in relapsing–remitting (RR) and secondary progressive (SP) MS patients by using a vision-based non-intrusive eye tracker. POM frequency was significantly lower (p < 0.001) in MS patients compared to normal controls. No differences between RR and SP-MS patients and no correlation between POM and expanded disability status scale (EDSS) score were found. This exploratory study suggests that our vision-based system is a new simple non-intrusive method showing impairment of POM values in MS patients, even in the absence of association with clinical disability (EDSS). Future works on larger cohorts of MS patients might validate this eye tracking in MS clinical practice.     

Survey of multiple sclerosis in northern California. Northern California MS Study Group.

A random sample of 493 multiple sclerosis (MS) patients registered with the Northern California Chapter of the National MS Society was surveyed by mail and subsequently interviewed with regard to their MS, life style, diet, medical treatment, family history, and insurance coverage. Of this sample, 168 patients (34%) returned completed questionnaires. The answers on the questionnaire were entered into a database and scores on the extended disability status scale (EDSS), the neurologic rating scale (NRS), the ambulation index (AI), and the mean disability scale (MDS) were determined from the patient's answers to a portion of the questionnaire using a previously validated conversion program. This survey population of 168 patients seemed to represent well both the random sample and the frame population from which it was drawn. Patients commonly experienced symptoms for which there are medical treatments currently available such as bladder symptoms, fatigue, spasticity, pain, and depression. Surprisingly, however, with the exception of spasticity, patients were only infrequently treated for these complaints. In addition, despite the recent approval of the beta-interferons and copolymer I in the treatment of MS, only 74% of the appropriate candidates for such treatment had these options discussed with them and only 45% ever actually received such treatment. Certain clinical features and dietary habits were strongly associated with both EDSS scores and total disability. Not unexpectedly, either a progressive disease course or the presence of neurological dysfunction in any one of a number of functional areas (e.g. bladder, vision, cognitive change, etc.) correlated with higher EDSS scores and greater total disability. Fatigue was also strongly correlated with disability. Indeed, fatigue accounted (in whole or in part) for 65% of the disability experienced by patients; an observation which only underscores the fact that fewer than one third of the patients who experience fatigue have ever been tried on medications. Interestingly, the only factors associated with lower EDSS scores and less total disability were exercise and alcohol consumption. Such associations from a single survey, however, do not establish causation. It is the purpose of this study to establish a baseline level of function within this survey population so that future surveys in the same set of individuals can allow a prospective assessment of how health outcome has influenced different aspects of the patient's medical care, lifestyle, and insurance coverage.     

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.     

Cognitive function alone is a poor predictor of health-related quality of life in employed patients with MS: results from a cross-sectional study

Objective: Depression, anxiety, disease severity, and cognitive functions impact on the quality of life of people with MS. However, the majority of studies were not based on multivariate models and did not target employed patients. The aim of this study was to investigate predictors of HRQoL in persons with MS in the workforce considering cognitive, psychological, disease severity, and disability-related variables. Methods: Cross-sectional study. Hierarchical block regression analyses were conducted to identify predictors of physical and mental components of HRQoL, measured with the MSQOL-54. Candidate predictors included cognitive functioning (a selection of Rao’s BRB-NT), sample features (age, education, MS duration), depressive symptoms (BDI-II), anxiety (STAI-Y), disability (WHODAS 2.0), and MS severity (EDSS): those that correlated with PCS and MCS with p < .250 and those that correlated with other predictors with coefficients >.800 were excluded from regression analyses. Results: In total, 181 patients (60.8% females, mean age 39.6, median EDSS 1.5) were included. In both models, cognitive variables had a poor explicative power. The models improved significantly when psychological, as well as, disease severity and disability variables were added. R² of complete models was 0.732 for the physical component, 0.697 for the mental one: BDI-II, STAI-State and, some WHODAS 2.0 scales were significant predictors of HRQoL. Conclusions: Monitoring anxiety, depressive symptoms, and level of disability through self-reported questionnaires may provide useful suggestions to improve the HRQoL of persons with MS in the workforce, permitting to address possible problems in the work context and plan corrective actions.     

Magnetic resonance imaging measures of brain and spinal cord atrophy correlate with clinical impairment in secondary progressive multiple sclerosis

BackgroundNeuroaxonal loss is a pathological substrate of disability in progressive multiple sclerosis (MS) and can be estimated in vivo by measuring tissue atrophy on magnetic resonance imaging (MRI). While there is some evidence that brain atrophy correlates better with disability than T2 lesion load in secondary progressive MS, the clinical relevance of atrophy within specific regions of the central nervous system requires further evaluation.MethodsClinical and MRI examinations were performed in 117 subjects with secondary progressive MS. MRI analysis included measures of normalized brain volume (NBV), normalized grey matter (NGMV) and white matter volume (NWMV), central cerebral volume (CCV), spinal cord cross-sectional area (SCCA), and brain T2 and T1 lesion volume. Clinical assessments included the expanded disability status scale (EDSS) and MS functional composite (MSFC).ResultsAll MRI measures correlated significantly with the MSFC score, with the strongest correlation being for the NBV (r = 0.47; P < 0.001). NBV and SCCA were the only significant independent predictors of the MSFC score in a stepwise regression model containing all the MRI measures, and SCCA was the only MRI measure to show a significant association with the EDSS. While NGMV had stronger correlations with the clinical variables than NWMV, NBV was more correlated with clinical impairment than either measure.ConclusionsThis data suggests that measures of atrophy, particularly of the whole brain and spinal cord, are relevant and useful disease markers in secondary progressive MS.     

Grasping multiple sclerosis: do quantitative motor assessments provide a link between structure and function?

Motor disability in MS is commonly assessed by the Expanded Disability Status Scale (EDSS). Categorical rating scales are limited by subjective error and inter-rater variability. Therefore, objective and quantitative measures of motor disability may be useful to supplement the EDSS in the setting of clinical trials. It was previously shown that grip-force-variability (GFV) is increased in MS. We hypothesized that GFV may be an objective measure of motor disability in MS. To investigate whether the increase in GFV in MS is correlated to the clinical disability as assessed by the EDSS and to microstructural changes in the brain as assessed by diffusion tensor imaging, GFV was recorded in a grasping and lifting task in 27 MS patients and 23 controls using a grip-device equipped with a force transducer. The EDSS was assessed by neurologists experienced in MS. Patients underwent diffusion tensor imaging at 3T to assess the fractional anisotropy (FA) of the cerebral white matter as a measure of microstructural brain integrity. GFV was increased in MS and correlated to changes in the FA of white matter in the vicinity of the somatosensory and visual cortex. GFV also correlated with the EDSS. GFV may be a useful objective measure of motor dysfunction in MS linked to disability and structural changes in the brain. Our data suggests that GFV should be further explored as an objective measure of motor dysfunction in MS. It could supplement the EDSS, e.g., in proof of concept studies.     

Impact of depression and disability on quality of life in Iranian patients with multiple sclerosis

Multiple sclerosis (MS) can influence all aspects of a patient's health. This study determines the main factors affecting quality of life (QoL) in Iranian MS patients. QoL (Multiple Sclerosis Impact Scale; MSIS-29), disability (Expanded Disability Status Scale; EDSS) and depression (Beck Depression Inventory; BDI) were assessed in 106 MS patients. EDSS, clinical course and MS duration significantly correlated with physical MSIS-29. Depression highly correlated with both physical and psychological MSIS-29. Regression analyses showed that depression and EDSS predicted physical health. Psychological health was predicted by depression. These findings highlight that depression and physical disability strongly influence QoL in Iranian MS patients.     

Improvement in strength following resistance training in MS patients despite varied disability levels

Strength and endurance data from 67 participants with multiple sclerosis (MS) were compared before, during and after a 6-month program of standardized resistance training. The hypothesis was that a standardized, structured resistance training exercise program improves strength in MS patients with different levels of disability. The range of EDSS scores was 1-8: (40% - EDSS of 1-4.5), (35% - EDSS of 5-7) (25% - EDSS of 7.5 or higher). This unique study evaluated patients with differing levels of disability for a change in strength and endurance following a 6-month training program. Data were analyzed by repeat measures and analysis of variables using Proc GLM in SAS to account for variability between subjects, and within subjects, due to repeated measures at 3 time points. Each treatment was blocked by disability class. Every within-treatment analysis was significant. Each exercise showed significant improvement in strength for participants, despite disability levels. Increases in strength followed parallel improvement pathways, at all disability levels. All but one treatment displayed highly significant improvement (p-value < 0.0001). The results demonstrated that all individuals with MS, despite disability levels, show parallel improvement in strength and endurance. This study supports the use of exercise, including resistance programs, for all MS patients.     

Volumes of brain atrophy and plaques correlated with neurological disability in secondary progressive multiple sclerosis.

The objectives of the present study was to correlate the segmented magnetic resonance imaging (MRI) volumes of intracranial cerebrospinal fluid (CSF) spaces (expressing the extent of brain atrophy) and cerebral plaques with the neurological disability in secondary progressive multiple sclerosis (MS). Earlier studies have mainly correlated MS plaques and neurological disability measured by expanded disability status scale (EDSS). The data on the association between brain atrophy and EDSS or regional functional scoring scale (RFSS) are very limited. We measured the volumes of intracranial CSF spaces in 28 patients with secondary progressive MS using MRI, and semiautomatic segmentation software. The volumes of T1-weighted hypointense and T2-weighted hyperintense MS plaques were also measured. In multiple regression analysis, increasing volumes of total (P=0.006) and relative (P=0.005) intracranial CSF spaces were significantly associated with worsening neurological disability as expressed by EDSS. No associations were found between these intracranial CSF space volumes and total RFSS scores. The mean volume of T2-weighted plaques showed a tendency to associate with total RFSS score (r=0.40, P=0.03), but no correlations were detected between T1- or T2-weighted plaque volumes and EDSS. The application of a new segmentation technique in quantifying intracranial cerebrospinal fluid spaces allowed an exact and sensitive way of assessing brain atrophy. The associations between brain atrophy and neurological disability expressed by EDSS suggests that the effect of MS therapies should be evaluated by measurement of brain atrophy.