A simple measure of cognitive reserve is relevant for cognitive performance in MS patients

Cognitive reserve (CR) contributes to preserve cognition despite brain damage. This theory has been applied to multiple sclerosis (MS) to explain the partial relationship between cognition and MRI markers of brain pathology. Our aim was to determine the relationship between two measures of CR and cognition in MS. One hundred and forty-seven MS patients were enrolled. Cognition was assessed using the Rao’s Brief Repeatable Battery and the Stroop Test. CR was measured as the vocabulary subtest of the WAIS-R score (VOC) and the number of years of formal education (EDU). Regression analysis included raw score data on each neuropsychological (NP) test as dependent variables and demographic/clinical parameters, VOC, and EDU as independent predictors. A binary logistic regression analysis including clinical/CR parameters as covariates and absence/presence of cognitive deficits as dependent variables was performed too. VOC, but not EDU, was strongly correlated with performances at all ten NP tests. EDU was correlated with executive performances. The binary logistic regression showed that only the Expanded Disability Status Scale (EDSS) and VOC were independently correlated with the presence/absence of CD. The lower the VOC and/or the higher the EDSS, the higher the frequency of CD. In conclusion, our study supports the relevance of CR in subtending cognitive performances and the presence of CD in MS patients.     

The relation between objective and subjective impairment in cognitive function among multiple sclerosis patients--the role of depression.

OBJECTIVE: To evaluate the relations between perceived cognitive function and objective cognitive deficit and to assess variables affecting perceived cognitive function among multiple sclerosis (MS) patients. METHODS: A cross sectional study of patients with MS. All patients were interviewed and the Expanded Disability Status Scale (EDSS) score was determined. The dependent variables were four items assessing perceived concentration and thinking, attention, memory, and whether others have noticed memory or concentration problems. The explanatory variables were age, sex, duration of disease, number of relapses in the last 2 years, EDSS score, depressive symptoms score (CES-D) and the domains of the Neurobehavioral Cognitive Status Examination (NCSE) assessing cognitive performance. Bivariate and then multivariate analysis were performed. RESULTS: One hundred and sixty-one MS patients were included. Mean age was 44.2 years (s.d. 11.3 years), mean EDSS score was 4.86 (s.d. 1.93). Seventy-two per cent of the patients had objective cognitive impairment and 51% reported decreased perceived cognitive function. In all models assessing perceived cognitive function we could explain only a small part of the variance (R2 ranged between 18-26%). In all these models depressive symptoms explained the highest portion of the variance (partial R2 ranging between 13-26%). The only domain of the NCSE that entered some of the models was calculation (partial R2 ranging between 3-7%). CONCLUSIONS: These findings emphasize the gap between objective and subjective assessment of cognitive function and the high correlation between perceived cognitive deficit and depressive symptoms.     

Psychometric study of Turkish version of Fatigue Impact Scale in multiple sclerosis patients

BACKGROUND: The aims of this study were to test the validity, test-retest reliability, and internal consistency of Turkish version of FIS; the variables affecting FIS score. MATERIALS AND METHODS: 71 MS patients and 68 healthy subjects were included to the study. RESULTS: Total FIS score and subscale scores were different statistically between MS patients and healthy volunteers in both first and second FIS applications (p<0.001). These results showed that FIS is validated in divergent direction. BDI score was higher in MS patients than healthy volunteers (p<0.001). There was no statistically significant difference between two study groups for cognitive subscale scores, after the effect of depression was eliminated (p>0.05). To assess the test-retest reliability, the scores of two FIS applications did not differ statistically (cognitive t=1.948 p>0.05, physical t=1.420 p=0.160, social t=1.470 p=0.146, total t=1.990 p=0.05). Intraclass correlation coefficients were 0.89 (99% confidence interval: 0.79-0.94) for cognitive, 0.95 (0.91-0.97) for physical, 0.91 (0.83-0.95) for social, and 0.93 (0.86-0.96) for total FIS scores (p<0.001). EDSS correlated with physical subscores in both applications of FIS. CONCLUSION: Turkish version of FIS, which is valid and reliable, seems an appropriate tool for the assessment of the effects of fatigue in Turkish MS population.     

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.     

Cognitive impairment after three decades of multiple sclerosis

Background: Population‐based studies of cognitive impairment in patients with multiple sclerosis (MS) with long disease duration are limited. The aim of this study was to evaluate long‐term outcome and the predictors of cognitive impairment in a cohort of patients with MS. Methods: Patients living in Oslo, Norway, with definite MS and onset in 1940–1980 alive on 1 May 2006 were included. Disability was assessed by Expanded Disability Status Scale (EDSS). Cognitive functioning was assessed in terms of psychomotor speed, attention, learning/memory and executive functions. Results: A total of 123 patients was included. EDSS was ≤3.0 in 26% and ≥6.0 in 60% after mean disease duration of 34.5 years. Cognitive impairment was found in 48% of the patients eligible for neuropsychological evaluation (n = 84). Typical pattern was moderate impairment within areas of information processing, attention and memory. In the univariate analysis, younger onset age was significantly associated with cognitive impairment (P = 0.014). Younger onset age (P = 0.017) and disease course (secondary progressive vs. relapsing‐remitting MS, P = 0.049) were significantly associated with cognitive impairment in the multivariate analysis. Conclusions: After three decades of disease, half of the MS patients experienced reduced cognitive functioning; however, nearly one‐third of the patients were only mildly disabled based on the EDSS. Younger onset age was associated with higher prevalence of cognitive impairment. A thorough evaluation of cognitive function in addition to EDSS is essential for evaluating long‐term impairment in patients with MS.     

Short-latency afferent inhibition predicts verbal memory performance in patients with multiple sclerosis

Background   The pathogenesis of cognitive deficits in multiple sclerosis (MS) patients is the subject of debate. A causative role of grey matter impairment has been suggested. Acetylcholinesterase inhibitors have been proposed in the treatment of cognitive impairment in MS. Short-latency afferent inhibition (SAI) is a cortical phenomenon assessed by a transcranial magnetic stimulation protocol that provides an in vivo index of central cholinergic function. Methods   We recruited 20 consecutive relapsing-remitting or secondary progressive MS patients showing normal upper limb somatosensory and motor evoked potentials. SAI of the left-hand motor cortex from median nerve stimuli was tested. A matched group of 20 healthy subjects was also assessed. All patients underwent neuropsychological assessment with Rao’s Brief Repeatable Battery (BRB). Multiple regression was performed on the number of failed tests and on scores of single BRB tests as dependent variables with Extended Disability Status Scale (EDSS) score, SAI, age, gender and disease duration as regressors. Patients with impaired SAI, were reassessed after a single oral dose of rivastigmine. Results   SAI was a significant predictor of the score in tests that assess verbal memory. EDSS score and age were found as predictors of the other BRB tests. SAI was significantly improved by oral rivastigmine. Conclusions   Our data confirm that cognitive impairment in MS is multifactorial. The performances in the subdomain of verbal memory are predicted by SAI. These results favour the hypothesis of grey matter involvement and suggest a role of acetylcholine dysfunction in the pathogenesis of some aspects of cognitive deficits in MS.     

Contribution of four lifelong factors of cognitive reserve on late cognition in normal aging and Parkinson’s disease

Introduction. Cognitive reserve (CR) was proposed to explain how individual differences in brain function help to cope with the effects of normal aging and neurodegenerative diseases. Education, professional solicitations, and engagement in leisure and physical activities across the lifetime are considered as major determinants of this reserve. Method. Using multiple linear regression analyses, we tested separately in healthy elderly and Parkinson’s disease (PD) populations to what extent cognitive performance in several domains was explained by (a) any of these four environmental lifespan variables; (b) demographic and clinical variables (age, gender, depression score, and, for the PD group, duration of disease and dopaminergic drugs). We also tested for an interaction, if any, between these lifespan variables and brain pathology indexed by global atrophy measured from high-resolution anatomical magnetic resonance imaging. Results. Age was negatively associated with cognitive performance in the PD group. In healthy elderly participants, we observed significant positive associations between cognitive performance and (a) education, (b) leisure activities, and (c) professional solicitation (decisional latitude). Furthermore, participants with greater brain atrophy benefited more from CR. In PD patients, education and professional solicitations contributed to cognitive performance but to a lesser extent than in controls. CR factors modulated the relationship between cognition and brain atrophy only in patients with a slight or moderate brain atrophy. Conclusions. Education is the CR factor that contributed the most to late cognitive functioning in both groups, closely followed by leisure activity in normal aging and professional solicitations in PD. Our results also provide evidence suggesting that the effects of CR does not express similarly in normal aging and PD. From a broader perspective, these results seem to indicate that CR factors the most consistently practiced across lifespan (education and professional solicitation) are those that are the more strongly associated to late cognitive efficiency.     

The percentage and clinical correlates of alexithymia in stable patients with schizophrenia

Alexithymia is a common, but less-recognized affective deficit in patients with schizophrenia. To date, no definitive conclusions have been drawn about the relationship between alexithymia and the clinical symptoms or their clinical correlates, particularly in stable patients with schizophrenia. The purpose of this study was to investigate the link between alexithymia and psychopathological symptoms, as well as any associated correlates, in stable patients with schizophrenia. A total of 435 Chinese patients with schizophrenia were recruited. The Positive and Negative Symptoms Scale (PANSS) was used to evaluate each patient’s psychopathological symptoms. The Toronto Alexithymia Scale (TAS-20) was used to measure alexithymia. The percentage of alexithymia was 35.2% in stable patients with schizophrenia. Compared to non-alexithymia patients, patients with alexithymia had higher PANSS total scores, negative subscores, depressive subscores, and cognitive subscores (all p < 0.05). Multivariate regression analysis revealed that the following variables were positively associated with TAS-20 total scores: PANSS negative subscores (β = 0.274, t = 3.198, p = 0.001) and PANSS depressive subscores (β = 0.366, t = 2.500, p = 0.013). Education years (β = – 0.453, t = – 2.824, p = 0.005) was negatively associated with TAS-20 total scores. Our results suggest that the percentage of alexithymia was relatively higher in stable patients with schizophrenia. Education levels, negative symptoms, and depressive symptoms were independently associated with alexithymia in this specific population.

     

Association of neocortical volume changes with cognitive deterioration in relapsing-remitting multiple sclerosis

BACKGROUND: We previously reported selective decreases of neocortical volumes in patients with early relapsing-remitting (RR) multiple sclerosis (MS) with mild cognitive impairment, with a good correlation between cortical volumes and cognitive measures. OBJECTIVE: To assess the relevance of gray matter changes over time to changes in cognition in RRMS. DESIGN: A longitudinal survey after 2.5 years. Each patient underwent a magnetic resonance imaging (MRI) protocol identical to that performed at baseline; cognitive performance was reassessed with the Rao Brief Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis. SETTING: Two university MS clinics. PATIENTS: Of 41 patients with RRMS who participated in the original cross-sectional study, 28 were available for the follow-up evaluation (18 women; mean +/- SD age, 37.1 +/- 8.9 years; mean +/- SD MS duration, 7.3 +/- 2.9 years; mean +/- SD Expanded Disability Status Scale score, 1.8 +/- 1.5). MAIN OUTCOME MEASURES: We measured the percentage of brain volume changes, normalized cortical volume (NCV) changes, and normalized deep gray matter volume changes on conventional T1-weighted MRIs and changes in lesion load on T2-weighted MRIs. The number of tests failed on the Rao Brief Repeatable Battery were used to classify the patients as cognitively deteriorating or stable or improving. RESULTS: We identified 12 of 28 cognitively deteriorating and 16 of 28 stable or improving patients. These subgroups did not differ in the mean +/- SD percentage of brain volume changes (-2.1% +/- 1.2% vs -1.3% +/- 1.3%; P = .11), normalized deep gray matter volume changes (-2.1 +/- 2.8 mL vs -0.6 +/- 3.1 mL; P = .60), and changes in lesion load on T2-weighted MRIs (1.9 +/- 2.6 mL vs 1.6 +/- 2.3 mL; P = .73). However, NCV changes were significantly higher in deteriorating than in stable or improving patients (-43.0 +/- 18.9 mL vs -17.8 +/- 26.6 mL; P = .007). In deteriorating patients, NCV changes were correlated with performance in a verbal fluency test (r = 0.73; P < .001). In a regression model, only NCV changes were significantly associated with deteriorating cognitive performance (odds ratio, 0.8; 95% confidence interval, 0.7-0.9). CONCLUSION: Progressive neocortical gray matter loss is relevant to MS-associated cognitive impairment and may represent a sensitive marker of deteriorating cognitive performance in RRMS.     

The Relationship Between Cognitive Reserve and Functional Ability is Mediated by Executive Functioning in Older Adults

It has been noted in the literature that cognitive reserve (CR) predicts future functional ability (FA), but the association between CR and current FA is rather limited. This investigation aimed to explicate this relationship, and hypothesized it would be mediated by executive functioning (EF). To best understand the relationship between CR and FA, we recruited and tested independent community-dwelling older adults (OAs). Bivariate correlations and hierarchical regressions were completed to determine the association between CR and FA. Both individual CR measures and a composite CR score were used. Mediation analyses were completed to examine our hypothesis that EF would mediate the CR and FA relationship. All measures of CR were positively related to and predictive of FA. Although the highest zero-order correlation across the independent CR proxies was between income and FA (r = .417), education accounted for the greatest amount of variance in FA, 8.3% after controlling for age and Mini-Mental State Examination performance. Furthermore, the CR composite had a higher correlation (r = .447) and accounted for more variance than any of the independent proxies. Complete mediation was found between a CR composite and FA via an internally consistent D-KEFS composite score (Cronbach’s α = .795). This suggests that as CR increases so does EF, which in turn improves FA. Thus, future investigations could determine the effect on FA in OAs by improving EF.     

Gender-related effect of clinical and genetic variables on the cognitive impairment in multiple sclerosis

Abstract. Background: Cognitive impairment may occur at any time during the course of multiple sclerosis (MS), and it is often a major cause of disability in patients with the disease. The APOE-4 allele is the major known genetic risk factor for late onset familial and sporadic Alzheimers Disease (AD), and it seems to be implicated in cognitive decline in normal elderly persons. Objective: To investigate the clinical and genetic variables that can be associated with the cognitive decline in patients with MS. Methods: Five-hundred and three patients with clinically definite MS underwent a battery of neuropsychological tests and, according to the number of failed tests, were divided into cognitively normal and impaired. All patients were genotyped for APOE gene polymorphisms. Results: Fifty-six percent of MS patients showed, to different extents, cognitive impairment. Cognitive decline was predominant in men and was associated with disease duration, Kurtzke Expanded Disability Status Scale (EDSS) score, a low level of education, and, interestingly, the 4 allele of the APOE gene. By contrast, cognitive impairment in women was independent of any investigated variable. Conclusion: The findings demonstrate that clinical and genetic factors play a role in men affected by MS developing cognitive impairment.This work was supported in part by a grant from FISM (Federazione Italiana Sclerosi Multipla).     

Is there a differential impact of fatigue and physical disability on quality of life in multiple sclerosis?

To investigate the quantitative impact of fatigue on health-related quality of life (HRQoL) in multiple sclerosis (MS) and to determine whether fatigue was related to HRQoL independently from bodily disability, data on HRQoL were ascertained for 87 patients with definite MS by using the SF-36. HRQoL scores and subscores were related to the basic MS disability score (EDSS) and further MS parameters, and to fatigue, which was assessed by using different fatigue scales. Factors related to predominantly physical but not mental HRQoL aspects were identified as related to EDSS, duration of disease, and age. Different fatigue scores did impact significantly on both physical and especially mental HRQoL. The influence of fatigue on physical HRQoL was independent from EDSS. Fatigue experience reduces HRQoL markedly and independently from EDSS. Therefore, fatigue assessment provides additional information to disability-derived scales such as the EDSS with relevant implications for therapeutic decisions.     

Health-related quality of life in secondary progressive multiple sclerosis

Common disability scales in multiple sclerosis (MS) are often weighted towards physical disability. Non-motor symptoms such as depression, fatigue and pain substantially influence wellbeing in MS. Health-related quality of life (HRQoL) measures the broader impact of MS and might indicate less obvious disease burdens. We analysed HRQoL, using the Nottingham Health Profile Part I (NHP-I), among 345 secondary progressive MS (SPMS) patients participating in a randomized trial of interferon-beta1a (IFN-beta1a), 22 mug subcutaneously weekly, or matching placebo. The results did not reveal any beneficial effect of IFN-beta1a in any outcome measure. NHP-I sub- and sum scores were compared for 217 population controls and correlated with demographic and clinical disease variables. SPMS patients had lower NHP-I sum and all subscores than the controls. Patients experiencing disease progression reported worse NHP-I sum scores. Increased fatigue, Expanded Disability Status Scale (EDSS) and Arm Index scores were independently associated with reduction in several NHP-I subscores. SPMS patients had significantly lower HRQoL than controls and physical disability (EDSS and Arm Index), disease progression and fatigue strongly influenced this. MS.     

认知储备对不同认知阶段脑白质高信号人群脑白质纤维束完整性的影响

目的 探讨认知储备（cognitive reserve,CR）对不同认知阶段脑白质高信号（white matter hyperintensity, WMH）患者白质纤维束完整性的影响。      

Health-related quality of life in patients with relapsing-remitting multiple sclerosis treated with subcutaneous interferon β-1a in Iran

Purpose: Multiple sclerosis (MS) requires long-term therapy and can affect many aspects of a patient's life, including quality of life. MS patients score lower on health-related quality of life (HRQoL) measures. The efficacy of subcutaneous interferon (IFN) β-1a has been extensively evaluated by using objective measures but its impact on HRQoL is currently unclear. In this observational study, we evaluated HRQoL of Iranian patients with relapsing-remitting MS (RRMS) treated with IFN β-1a by using short-form 36 (SF-36) and multiple sclerosis international quality of life (MusiQoL) questionnaires. Methods: Four hundred recruited RRMS patients were treated with human serum album free IFN β-1a for 1 year. Patients were required to fill in SF-36 and MusiQoL questionnaires at the first visit and at each follow-up visit. Expanded disability status scale (EDSS) evaluation was performed at baseline and at each visit. Comparisons in HRQoL between visits were calculated using Cohen's d effect size. The relationship between change in EDSS score and the score of each questionnaire was calculated using Pearson correlation coefficients. Results: Three-hundred and eighty three completed the study. Two-hundred and thirty nine were female. Mean (SD) age was 28.75 (±5.49). After 1 year, overall MusiQoL Index score effect size was ?0.16 and SF-36 physical component and mental component showed overall effect sizes of ?0.28 and ?0.53, respectively. Mean (range) EDSS change was 1 (1–4). Three-hundred and seventy four were clinically stable with mean (range) EDSS change of 0.1 (?2–0.5). Increase in EDSS was linked to a decrease in both MusiQoL and SF-36. Conclusion: We found that, HRQoL did not change significantly over the first year of therapy. Furthermore, decreases in HRQoL were inversely correlated with increases in EDSS score.     

Quality of life in multiple sclerosis patients with urinary disorders: reliability and validity of the Turkish version of King’s Health Questionnaire

MS patients frequently present with urinary system symptoms, which have a negative effect on the quality life. The aim of our study was to demonstrate the validity and reliability of the Turkish King’s Health Questionnaire (KHQ) in MS patients. The study included 37 patients. For analysis of test–retest reliability, the Turkish version of the KHQ developed and the “translation-back translation” method was performed. To assess the validity of these results, Multiple Sclerosis Quality of Life Scale (MQoL-54) and Expanded Disability Status Scale (EDSS) were used. The internal consistency (intra-class correlation coefficient: 0.59–0.94) and test–retest reliability (Cronbach’s α-score 0.59–0.94) of KHQ were found to be high (p < 0.05). A significant correlation was detected between most of the KHQ subscores and the physical and mental MQoL-54 and EDSS (total and bowel/bladder, p < 0.05) subscores. The KHQ may be used to determine the effect of incontinence on the quality of life for MS patients.     

A longitudinal uncontrolled study of cerebral gray matter volume in patients receiving natalizumab for multiple sclerosis

Objective: Brain atrophy in multiple sclerosis (MS) selectively affects gray matter (GM), which is highly relevant to disability and cognitive impairment. We assessed cerebral GM volume (GMV) during one year of natalizumab therapy. Design/methods: Patients with relapsing–remitting (n = 18) or progressive (n = 2) MS had MRI ～1 year apart during natalizumab treatment. At baseline, patients were on natalizumab for (mean ± SD) 16.6 ± 10.9 months with age 38.5 ± 7.4 and disease duration 9.7 ± 4.3 years. Results: At baseline, GMV was 664.0 ± 56.4 ml, Expanded Disability Status Scale (EDSS) score was 2.3 ± 2.0, timed 25-foot walk (T25FW) was 6.1±3.4 s; two patients (10%) had gadolinium (Gd)-enhancing lesions. At follow-up, GMV was 663.9 ± 60.2 mL; EDSS was 2.6 ± 2.1 and T25FW was 5.9 ± 2.9 s. One patient had a mild clinical relapse during the observation period (0.052 annualized relapse rate for the entire cohort). No patients had Gd-enhancing lesions at follow-up. Linear mixed-effect models showed no significant change in annualized GMV [estimated mean change per year 0.338 mL, 95% confidence interval ?9.66, 10.34, p = 0.94)], GM fraction (p = 0.92), whole brain parenchymal fraction (p = 0.64), T2 lesion load (p = 0.64), EDSS (p = 0.26) or T25FW (p = 0.79). Conclusions: This pilot study shows no GM atrophy during one year of natalizumab MS therapy. We also did not detect any loss of whole brain volume or progression of cerebral T2 hyperintense lesion volume during the observation period. These MRI results paralleled the lack of clinical worsening.     

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.     

Prognostic value of multimodal evoked potentials in multiple sclerosis: the EP score

Evoked potentials (EPs) have long been used as diagnostic tools in multiple sclerosis (MS), although their importance decreased as magnetic resonance imaging (MRI) became available. However, the prognostic value of EPs in MS has not been completely established. The aim of the study was to analyze the prognostic significance of EPs in a cohort of MS cases. From the Verona University Hospital MS Clinic database we retrospectively identified 80 MS patients who underwent a complete neurophysiological evaluation, including visual, brain stem, somatosensory and motor EPs and who were followed for at least 5 years after the study. EPs abnormalities were quantified through an index of global EPs alteration (EP score). The relationship between EP score and disability in terms of Expanded Disability Status Scale (EDSS) was analyzed by the Kaplan–Meier survival method and Spearman ρ correlation coefficient. ROC curves were used to determine the best EP score cut off to predict different EDSS endpoints. For each endpoint, sensitivity, specificity, positive and negative predictive value of EP score were calculated. We found a significant correlation (p < 0.001) between EP score and EDSS score at the time of neurophysiological study and at 1, 3 and 5 years of follow-up, particularly for motor and somatosensory EPs. Kaplan–Meier curves confirmed an increased risk of disability in those patients with EP score higher than the median value. EP score of 8 or 9 showed the highest sensitivity and specificity in predicting EDSS 4.0 and 6.0. EPs are reliable procedures to predict disability in MS patients. The correlation between EPs abnormalities and EDSS is higher than between conventional MRI and EDSS.     

Neocortical volume decrease in relapsing-remitting multiple sclerosis with mild cognitive impairment

The aim of the study was to assess neocortical changes and their relevance to cognitive impairment in early relapsing-remitting multiple sclerosis (RRMS). Conventional magnetic resonance was acquired in 41 RRMS patients and 16 demographically matched normal controls (NC). An automated analysis tool was used to obtain measures of cortical brain volumes normalized for head size. Neuropsychological performance of MS patients was assessed through the Rao's Brief Repeatable Battery. We identified 18 cognitively preserved (MS-cp) and 23 cognitively impaired (MS-ci) MS patients. Values of normalized cortical volumes (NCV) in the whole MS sample were lower than those in the NC group (p=0.01). MS-ci patients showed NCV values lower (p=0.02) than did both MS-cp patients and NC. Moreover, we found a positive correlation between NCV values and measures of verbal memory (r=0.51, p=0.02), verbal fluency (r=0.51, p=0.01) and attention/concentration (r=0.65, p<0.001) in MS-ci patients. Furthermore, NCV values were significantly decreased in patients who scored lower on a greater number of tests (r=-0.58, p<0.01) in the MS-ci group. Only MS-ci patients had cortical atrophy significantly correlated with a poorer neuropsychological performance. Grey matter pathology may contribute to the development of cognitive impairment in MS from the earliest stages of the disease.