BACKGROUND: Although there is evidence that shows worse cognitive functioning in male patients with multiple sclerosis (MS), the role of brain pathology in this context is under-investigated. OBJECTIVE: To investigate sex differences in cognitive performance of MS patients, in the context of brain pathology and disease burden. METHODS: Brain MRI, neurological examination, neuropsychological assessment (Brief International Cognitive Assessment in MS-BICAMS, and Paced Auditory Verbal Learning Test-PASAT), and patient-reported outcome questionnaires were performed/administered in 1052 MS patients. RESULTS: Females had higher raw scores in the Symbol Digit Modalities Test (SDMT) (57.0 vs. 54.0; p < 0.001) and Categorical Verbal Learning Test (CVLT) (63.0 vs. 57.0; p < 0.001), but paradoxically, females evaluated their cognitive performance by MS Neuropsychological Questionnaire as being worse (16.6 vs 14.5, p = 0.004). Females had a trend for a weaker negative correlation between T2 lesion volume and SDMT ([Formula: see text] = - 0.37 in females vs. - 0.46 in men; interaction p = 0.038). On the other hand, women had a trend for a stronger correlation between Brain Parenchymal Fraction (BPF) and a visual memory test (Spearman's [Formula: see text] = 0.31 vs. 0.21; interaction p = 0.016). All these trends were not significant after correction for false discovery rate. CONCLUSIONS: Although, females consider their cognition as worse, males had at a group level slightly worse verbal memory and information processing speed. However, the sex differences in cognitive performance were smaller than the variability of scores within the same sex group. Brain MRI measures did not explain the sex differences in cognitive performance among MS patients.

• Klíčová slova
• Brain atrophy, Cognition, Lesion volume, MRI, Multiple sclerosis, Sex,
• MeSH
• kognice MeSH
• kognitivní dysfunkce * MeSH
• kognitivní poruchy * diagnóza   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek diagnostické zobrazování   MeSH
• neuropsychologické testy MeSH
• pohlavní dimorfismus MeSH
• roztroušená skleróza * komplikace   diagnostické zobrazování   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Impairment of higher language functions associated with natural spontaneous speech in multiple sclerosis (MS) remains underexplored. OBJECTIVES: We presented a fully automated method for discriminating MS patients from healthy controls based on lexical and syntactic linguistic features. METHODS: We enrolled 120 MS individuals with Expanded Disability Status Scale ranging from 1 to 6.5 and 120 age-, sex-, and education-matched healthy controls. Linguistic analysis was performed with fully automated methods based on automatic speech recognition and natural language processing techniques using eight lexical and syntactic features acquired from the spontaneous discourse. Fully automated annotations were compared with human annotations. RESULTS: Compared with healthy controls, lexical impairment in MS consisted of an increase in content words (p = 0.037), a decrease in function words (p = 0.007), and overuse of verbs at the expense of noun (p = 0.047), while syntactic impairment manifested as shorter utterance length (p = 0.002), and low number of coordinate clause (p < 0.001). A fully automated language analysis approach enabled discrimination between MS and controls with an area under the curve of 0.70. A significant relationship was detected between shorter utterance length and lower symbol digit modalities test score (r = 0.25, p = 0.008). Strong associations between a majority of automatically and manually computed features were observed (r > 0.88, p < 0.001). CONCLUSION: Automated discourse analysis has the potential to provide an easy-to-implement and low-cost language-based biomarker of cognitive decline in MS for future clinical trials.

• Klíčová slova
• automated linguistic analysis, language, multiple sclerosis, nature language processing, spontaneous discourse,
• Publikační typ
• časopisecké články MeSH

The clinical course of multiple sclerosis (MS) is highly variable among patients, thus creating important challenges for the neurologist to appropriately treat and monitor patient progress. Despite some patients having apparently similar symptom severity at MS disease onset, their prognoses may differ greatly. To this end, we believe that a proactive disposition on the part of the neurologist to identify prognostic "red flags" early in the disease course can lead to much better long-term outcomes for the patient in terms of reduced disability and improved quality of life. Here, we present a prognosis tool in the form of a checklist of clinical, imaging and biomarker parameters which, based on consensus in the literature and on our own clinical experiences, we have established to be associated with poorer or improved clinical outcomes. The neurologist is encouraged to use this tool to identify the presence or absence of specific variables in individual patients at disease onset and thereby implement sufficiently effective treatment strategies that appropriately address the likely prognosis for each patient.

• Klíčová slova
• biomarkers, clinical parameters, evoked potentials, magnetic resonance imaging (MRI), multiple sclerosis, optical coherence tomography, prognosis, treatment,
• MeSH
• biologické markery MeSH
• kvalita života MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• prognóza MeSH
• recidiva MeSH
• roztroušená skleróza * diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• biologické markery MeSH

BACKGROUND: A percent brain volume change (PBVC) cut-off of -0.4% per year has been proposed to distinguish between pathological and physiological changes in multiple sclerosis (MS). Unfortunately, standardized PBVC measurement is not always feasible on scans acquired outside research studies or academic centers. Percent lateral ventricular volume change (PLVVC) is a strong surrogate measure of PBVC, and may be more feasible for atrophy assessment on real-world scans. However, the PLVVC rate corresponding to the established PBVC cut-off of -0.4% is unknown. OBJECTIVE: To establish a pathological PLVVC expansion rate cut-off analogous to -0.4% PBVC. METHODS: We used three complementary approaches. First, the original follow-up-length-weighted receiver operating characteristic (ROC) analysis method establishing whole brain atrophy rates was adapted to a longitudinal ventricular atrophy dataset of 177 relapsing-remitting MS (RRMS) patients and 48 healthy controls. Second, in the same dataset, SIENA PBVCs were used with non-linear regression to directly predict the PLVVC value corresponding to -0.4% PBVC. Third, in an unstandardized, real world dataset of 590 RRMS patients from 33 centers, the cut-off maximizing correspondence to PBVC was found. Finally, correspondences to clinical outcomes were evaluated in both datasets. RESULTS: ROC analysis suggested a cut-off of 3.09% (AUC = 0.83, p < 0.001). Non-linear regression R2 was 0.71 (p < 0.001) and a - 0.4% PBVC corresponded to a PLVVC of 3.51%. A peak in accuracy in the real-world dataset was found at a 3.51% PLVVC cut-off. Accuracy of a 3.5% cut-off in predicting clinical progression was 0.62 (compared to 0.68 for PBVC). CONCLUSIONS: Ventricular expansion of between 3.09% and 3.51% on T2-FLAIR corresponds to the pathological whole brain atrophy rate of 0.4% for RRMS. A conservative cut-off of 3.5% performs comparably to PBVC for clinical outcomes.

• Klíčová slova
• Brain atrophy, Multiple sclerosis, NEDA, Pathological cutoff, Ventricular volume,
• MeSH
• databáze faktografické statistika a číselné údaje   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• nelineární dynamika MeSH
• počítačové zpracování obrazu MeSH
• posuzování pracovní neschopnosti MeSH
• progrese nemoci MeSH
• referenční hodnoty MeSH
• relabující-remitující roztroušená skleróza diagnostické zobrazování   patologie   MeSH
• ROC křivka MeSH
• stupeň závažnosti nemoci MeSH
• ventriculi laterales diagnostické zobrazování   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVE: To investigate whether the strength of the association between magnetic resonance imaging (MRI) metrics and cognitive outcomes differs between various multiple sclerosis subpopulations. METHODS: A total of 1052 patients were included in this large cross-sectional study. Brain MRI (T1 and T2 lesion volume and brain parenchymal fraction) and neuropsychological assessment (Brief International Cognitive Assessment for Multiple Sclerosis and Paced Auditory Serial Addition Test) were performed. RESULTS: Weak correlations between cognitive domains and MRI measures were observed in younger patients (age≤30 years; absolute Spearman's rho = 0.05-0.21), with short disease duration (<2 years; rho = 0.01-0.21), low Expanded Disability Status Scale [EDSS] (≤1.5; rho = 0.08-0.18), low T2 lesion volume (lowest quartile; <0.59 mL; rho = 0.01-0.20), and high brain parenchymal fraction (highest quartile; >86.66; rho = 0.01-0.16). Stronger correlations between cognitive domains and MRI measures were observed in older patients (age>50 years; rho = 0.24-0.50), with longer disease duration (>15 years; rho = 0.26-0.53), higher EDSS (≥5.0; rho = 0.23-0.39), greater T2 lesion volume (highest quartile; >5.33 mL; rho = 0.16-0.32), and lower brain parenchymal fraction (lowest quartile; <83.71; rho = 0.13-0.46). The majority of these observed results were confirmed by significant interactions (P ≤ 0.01) using continuous variables. INTERPRETATION: The association between structural brain damage and functional cognitive impairment is substantially weaker in multiple sclerosis patients with a low disease burden. Therefore, disease stage should be taken into consideration when interpreting associations between structural and cognitive measures in clinical trials, research studies, and clinical practice.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, which often causes progressive neurological disability. In addition to motor and sensory dysfunction, cognitive decline and fatigue are frequent manifestations of the disease. Fatigue is probably the most common symptom, with up to 90% of MS individuals reporting fatigue at some point. Cognitive impairment affects about 50% of patients and may be present at all MS stages. The aim of this observational study was to evaluate changes in cognition, fatigue, and disability status in 300 relapsing-remitting MS (RRMS) patients, treated with subcutaneous (sc) interferon (IFN) β-1a over 2 years. METHODS: The study was designed as an observational, multicentre, prospective, single-arm, phase IV study carried out in 13 MS centres in the Czech Republic. Cognition status was assessed using the Paced Auditory Serial Addition Task (PASAT), fatigue using the Fatigue Descriptive Scale (FDS), and disability using the Expanded Disability Status Scale (EDSS), at baseline, and after 6, 12 and 24 months. The percentage of patients with changed versus stable cognition, fatigue status and disability was calculated at each time point and the changes in these scores were evaluated. RESULTS: The proportion of patients with cognitive improvement was higher compared with those with a stable or decreased PASAT scores at all time points, and the average cognitive performance improved during the follow-up period. Also the proportion of patients with stable or improved fatigue and EDSS scores was higher compared with those in which FDS or EDSS scores declined, this was found at all time points of the analysed sample. However, the direct effect of IFN β-1a on cognition and fatigue cannot be concluded from this study. CONCLUSIONS: The results of this observational study have demonstrated a stable or improved cognitive performance, fatigue status, and disability level in the majority of RRMS patients treated with sc IFN β-1a over a two-year follow-up period, in a real life setting, in the Czech Republic.

• Klíčová slova
• cognitive impairment, fatigue, interferon β-1a, multiple sclerosis, treatment,
• Publikační typ
• časopisecké články MeSH

Cognitive impairment (CI) may occur in clinically isolated syndrome (CIS) patients. While the relationship between CI and magnetic resonance imaging (MRI) has been investigated extensively in multiple sclerosis (MS), MRI correlates of CI in CIS patients are unknown. To investigate the evolution of CI and to determine brain MRI structural correlates associated with CI in CIS patients. This prospective 24-month observational study examined 81 CIS patients treated with 30 µg of intramuscular interferon beta 1a once a week. MRI acquisition and neuropsychological (NP) assessment were performed at baseline, 6, 12 and 24 months. Participants were tested with Czech-validated version of Minimal Assessment of Cognitive Function in MS battery and MRI measures of lesion activity and burden, and global, tissue-specific and regional brain atrophy were performed. Over 24 months, 36 CIS patients developed clinically definite MS (CDMS). CI was observed in 10 (12.3 %) CIS patients at baseline and at the 24 months follow-up. Eight CIS patients changed their CI status over the follow-up (four improved and four worsened). No significant difference in development of CI was detected between stable CIS patients and those who developed CDMS. In multivariate regression and mixed-effect model analyses, no significant relationship was found between NP and MRI parameters. The lack of significant relationship between MRI metrics and cognition in this group of CIS patients could be attributed to several factors including the cognitive reserve, effect of disease-modifying therapy and relatively short follow-up period.

• MeSH
• demyelinizační nemoci farmakoterapie   imunologie   patologie   psychologie   MeSH
• dospělí MeSH
• interferon beta 1a MeSH
• interferon beta aplikace a dávkování   farmakologie   MeSH
• kognice účinky léků   MeSH
• kognitivní dysfunkce farmakoterapie   imunologie   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mozek patologie   MeSH
• následné studie MeSH
• neuropsychologické testy MeSH
• progrese nemoci MeSH
• prospektivní studie MeSH
• roztroušená skleróza farmakoterapie   imunologie   patologie   psychologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• interferon beta 1a MeSH
• interferon beta MeSH

Traditionally, multiple sclerosis has been viewed as a disease predominantly affecting white matter. However, this view has lately been subject to numerous changes, as new evidence of anatomical and histological changes as well as of molecular targets within the grey matter has arisen. This advance was driven mainly by novel imaging techniques, however, these have not yet been implemented in routine clinical practice. The changes in the grey matter are related to physical and cognitive disability seen in individuals with multiple sclerosis. Furthermore, damage to several grey matter structures can be associated with impairment of specific functions. Therefore, we conclude that grey matter damage - global and regional - has the potential to become a marker of disease activity, complementary to the currently used magnetic resonance markers (global brain atrophy and T2 hyperintense lesions). Furthermore, it may improve the prediction of the future disease course and response to therapy in individual patients and may also become a reliable additional surrogate marker of treatment effect.

• MeSH
• atrofie MeSH
• kognitivní poruchy * patologie   patofyziologie   MeSH
• lidé MeSH
• mozek * patologie   patofyziologie   MeSH
• mozková kůra patologie   patofyziologie   MeSH
• progrese nemoci MeSH
• roztroušená skleróza * patologie   patofyziologie   MeSH
• zánět * patologie   patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH