Absence of BOLD adaptation in chronic fatigue syndrome revealed by task functional MRI.

Neurological symptoms are central to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), yet its underlying neurophysiological mechanisms remain elusive. We examined a neglected aspect of task-based functional MRI, focusing on how blood oxygenation level-dependent (BOLD) signals alter during cognitive tasks in ME/CFS. This prospective observational study utilised MRI scans on ME/CFS participants and healthy controls (HCs) with sedentary lifestyles (ACTRN12622001095752). Participants completed two blocks of a Symbol Digit Modalities Test, with 30 trials per block split into two sets. The fMRI signal changes between blocks and sets were compared within and between groups. Thirty-four ME/CFS participants (38 years ± 10; 27 women) and 34 HCs (38 ± 10; 27 women), were evaluated. In the second task block, ME/CFS participants exhibited increased activation in the right postcentral gyrus, contrasting with decreased activation in multiple regions in HCs. These results were further confirmed by significantly higher bilateral dynamic changes (2nd vs 1st set) in the motor, sensory and cognitive cortex in ME/CFS compared to HCs and significant correlations between those changes in the left primary motor cortex with fatigue severities. BOLD adaptation, potentially improving energy economy, was absent in ME/CFS, which may provide an underlying neurophysiological process in ME/CFS.

Influence of Education, Cognition, and Physical Disability on Quality of Life of Romanian Patients with Multiple Sclerosis-A Cohort Study.

Background and Objectives: objective measures of disability and neurological impairmentare used to search for disease activity and monitor disease evolution in multiple sclerosis (MS). These are sometimes in disagreement with subjective quality-of-life measures. We aimed to establish the relations between the Multiple Sclerosis Quality of Life instrument (MSQOL-54) and objective measures of neurological impairment. Materials and Methods: 107 patients with MS were evaluated with the Single Digit Modalities Test (SDMT) for cognition, Nine Holes Peg Test (9HPT) for upper limb function, 25 Feet Walk Test (25FWT) for gait, and EDSS for global disability in a cohort study. Age and education level were recorded as sociodemographic factors. Results: the median EDSS was 3.5 (IQR 2.5); average SDMT score was 30.38 ± 13.54; and 9HPT speed was significantly higher for the dominant upper limb (0.3 ± 0.1 pegs/s versus 0.28 ± 0.11 pegs/s) (p = 0.016). The mental health composite score of the MSQOL-54 correlated with the SDMT, education level, and EDSS. Education level correlated with cognition and quality of life. The physical health composite score of the MSQOL-54 correlated with motor-function parameters and with SDMT. The motor-function parameters correlated well among themselves. A linear regression model found an important influence of SDMT and education level on the mental health composite score of the MSQOL-54. Although the linear regression model predicting the physical health composite score from physical disability parameters was statistically sound, none of the determinants had a significant individual influence. Conclusions: the subscores of the MSQOL-54 correlated well with the objective parameters. The strongest correlations were those with the cognitive function. Correlations with physical disability were less powerful, probably reflecting their indirect and more limited influence on quality of life compared to cognition and perception of disability.

Symbol Digit Modalities Test in progressive multiple sclerosis.

INTRODUCTION: The Symbol Digit Modalities Test (SDMT) is a highly sensitive neuropsychological tool used for the assessment of information processing speed (IPS) in various neurological disorders. STATE OF THE ART: In this review, we have focused on the current knowledge regarding the use of SDMT selectively in the evaluation of progressive multiple sclerosis (PMS) patients. A literature review was performed regarding the application of SDMT in PMS, with a focus on the primary progressive and secondary progressive subtypes. Relationships of diverse disease-associated factors with SDMT have been described, including disease course, imaging findings, molecular biomarkers, treatment and others. CLINICAL IMPLICATIONS: SDMT is a very useful and easily applicable instrument in the diagnostic armamentarium of neurologists and neuropsychologists. It is especially valuable in the evaluation of PMS patients, in whom the prevalence of IPS deficits is higher than in relapsing-remitting multiple sclerosis subjects or in healthy individuals. FUTURE DIRECTIONS: An emphasis should be laid on larger study groups and differentiating between individual PMS subtypes and their separate analysis in the context of cognitive assessment.

Predictors of relapse severity in multiple sclerosis.

BACKGROUND: The severity of relapses is one of the determinants of residual disability in multiple sclerosis (MS), contributing to the final progressive state. However, the factors that predict the severity of relapses are not fully understood. AIM: To predict relapse severity in MS and investigate the relationship between relapse severity and the degree of improvement in physical, cognitive, and social tests. METHODS: This observational single-center study prospectively assesses relapse severity in patients with MS. Relapses were classified as mild, moderate, and severe. Before relapse treatment and 1 month into remission four physical tests, four cognitive tests, and six surveys were performed. Multinomial regression analyses were applied to predict relapse severity. RESULTS: A total of 126 relapses were studied prospectively. Twenty-two were lost to follow-up. Multiple sclerosis International Quality of Life (MusiQol) questionnaire (r = 0.28, p = 0.006) and Symbol Digit Modalities Test (SDMT, r = 0.23, p = 0.022) improvement statuses were correlated with the severity of the relapse. Higher cases with improvement were observed in the severe relapse group on both MusiQol and SDMT, but no difference for those with a mild relapse. In the predictive model, only disease duration [Odds Ratio (OR) 0.808 95% confidence interval (CI) 0.691 to 0.945; p = 0.008] and Body Mass Index (BMI, OR 1.148 95% CI 1.018 to 1.294; p = 0.024) were associated with relapse severity. CONCLUSION: Only disease duration was found to be predictive of relapse severity among disease-related variables. On the other hand, BMI may be a modifiable patient-related factor to consider in the management of exacerbations in MS.

Differences in resting state functional connectivity relative to multiple sclerosis and impaired information processing speed.

Background: Fifty-one percent of individuals with multiple sclerosis (MS) develop cognitive impairment (CI) in information processing speed (IPS). Although IPS scores are associated with health and well-being, neural changes that underlie IPS impairments in MS are not understood. Resting state fMRI can provide insight into brain function changes underlying impairment in persons with MS. Objectives: We aimed to assess functional connectivity (FC) differences in (i) persons with MS compared to healthy controls (HC), (ii) persons with both MS and CI (MS-CI) compared to HC, (iii) persons with MS that are cognitively preserved (MS-CP) compared to HC, (iv) MS-CI compared to MS-CP, and (v) in relation to cognition within the MS group. Methods: We included 107 participants with MS (age 49.5 ± 12.9, 82% women), and 94 controls (age 37.9 ± 15.4, 66% women). Each participant was administered the Symbol Digit Modalities Test (SDMT) and underwent a resting state fMRI scan. The MS-CI group was created by applying a z-score cut-off of ≤-1.5 to locally normalized SDMT scores. The MS-CP group was created by applying a z-score of ≥0. Control groups (HCMS-CI and HCMS-CP) were based on the nearest age-matched HC participants. A whole-brain ROI-to-ROI analysis was performed followed by specific contrasts and a regression analysis. Results: Individuals with MS showed FC differences compared to HC that involved the cerebellum, visual and language-associated brain regions, and the thalamus, hippocampus, and basal ganglia. The MS-CI showed FC differences compared to HCMS-CI that involved the cerebellum, visual and language-associated areas, thalamus, and caudate. SDMT scores were correlated with FC between the cerebellum and lateral occipital cortex in MS. No differences were observed between the MS-CP and HCMS-CP or MS-CI and MS-CP groups. Conclusion: Our findings emphasize FC changes of cerebellar, visual, and language-associated areas in persons with MS. These differences were apparent for (i) all MS participants compared to HC, (ii) MS-CI subgroup and their matched controls, and (iii) the association between FC and SDMT scores within the MS group. Our findings strongly suggest that future work that examines the associations between FC and IPS impairments in MS should focus on the involvement of these regions.

Role of white matter in cognitive impairment among relapsing remitting multiple sclerosis patients.

BACKGROUND: Multiple Sclerosis (MS) associated cognitive impairment is believed to be mostly connected with damage to gray matter. The contribution of white matter is still poorly understood. We aim to examine the relationship between cognition and white matter tracts among relapsing remitting MS (RRMS) patients. METHODS: Thirty RRMS patients were selected undergo the (3-seconds-interstimulus-interval paced auditory serial addition test) PASAT-3, the (symbol digit modalities test (SDMT) and full-brain MRI scans on a SIEMENS 3 Tesla Verio scanner. Diffusion Tensor Imaging (DTI) parameters, such as fractional anisotropy (FA) and mean diffusivity (MD) were examined in 37 white matter (WM) tracts. WM tracts were selected from the association pathways, projection pathways, commissural pathways by applying Human Connectome project (HCP)842 tractography atlas after DTI data reconstruction and registration to HCP1065 diffusion template in DSI Studio (version March 2021) In SPSS v26, Spearman's rank correlation analysis was used to examine the connection between DTI WM tracts and cognitive scores. The power of the study was increased by using false discovery rate (FDR) software. RESULTS: The mean scores on the PASAT-3 and SDMT were 31.5 ± 12.8 and 46.9 ± 16.7 respectively. Better cognitive performance was correlated to higher FA values, while lower cognitive function was correlated to higher MD values. There was a positive correlation between FA values in the right medial lemniscus and superior cerebellar peduncle and SDMT scores (p 0.05). Additionally, there was a trend for significance between the FA values in the left corticothalamic tract and SDMT scores. MD values in the superior cerebellar peduncle, left arcuate Fasciculus and left extreme capsule were negatively correlated with SDMT scores (p<0.05). PASAT-3 scores were negatively correlated with MD values in the right cerebellum, however, there was no significant correlation between PASAT-3 and FA values. CONCLUSIONS: White matter tracts, particularly the superior cerebellar peduncle, contribute to the cognitive impairment in RRMS. Larger sample sizes for longitudinal research are necessary.

Establishing the consistency of a voice recognition symbol digit modalities test analogue.

BACKGROUND: We previously demonstrated the convergent validity of a fully automated voice recognition analogue of the Symbol Digit Modalities Test (VR-SDMT) for evaluating processing speed in people with multiple sclerosis (pwMS). OBJECTIVE/METHODS: We aimed to replicate these results in 54 pwMS and 18 healthy controls (HCs), demonstrating the VR-SDMT's reliability. RESULTS: Significant correlations were found between the VR-SDMT and the traditional oral SDMT in the multiple sclerosis (MS) (r = -0.771, p < 0.001) and HC (r = -0.785, p < 0.001) groups. CONCLUSION: Taken collectively, our two studies demonstrate the reliability and validity of the VR-SDMT for assessing processing speed in pwMS.

Oculomotor analysis to assess brain health: preliminary findings from a longitudinal study of multiple sclerosis using novel tablet-based eye-tracking software.

A growing body of evidence supports the link between eye movement anomalies and brain health. Indeed, the oculomotor system is composed of a diverse network of cortical and subcortical structures and circuits that are susceptible to a variety of degenerative processes. Here we show preliminary findings from the baseline measurements of an ongoing longitudinal cohort study in MS participants, designed to determine if disease and cognitive status can be estimated and tracked with high accuracy based on eye movement parameters alone. Using a novel gaze-tracking technology that can reliably and accurately track eye movements with good precision without the need for infrared cameras, using only an iPad Pro embedded camera, we show in this cross-sectional study that several eye movement parameters significantly correlated with clinical outcome measures of interest. Eye movement parameters were extracted from fixation, pro-saccade, anti-saccade, and smooth pursuit visual tasks, whereas the clinical outcome measures were the scores of several disease assessment tools and standard cognitive tests such as the Expanded Disability Status Scale (EDSS), Brief International Cognitive Assessment for MS (BICAMS), the Multiple Sclerosis Functional Composite (MSFC) and the Symbol Digit Modalities Test (SDMT). Furthermore, partial least squares regression analyses show that a small set of oculomotor parameters can explain up to 84% of the variance of the clinical outcome measures. Taken together, these findings not only replicate previously known associations between eye movement parameters and clinical scores, this time using a novel mobile-based technology, but also the notion that interrogating the oculomotor system with a novel eye-tracking technology can inform us of disease severity, as well as the cognitive status of MS participants.

Optical coherence tomography versus other biomarkers: Associations with physical and cognitive disability in multiple sclerosis.

BACKGROUND: Optical coherence tomography (OCT) is a biomarker of neuroaxonal loss in multiple sclerosis (MS). OBJECTIVE: The objective was to assess the relative role of OCT, next to magnetic resonance imaging (MRI) and serum markers of disability in MS. METHODS: A total of 100 patients and 52 controls underwent OCT to determine peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform layers (GCIPL). Serum neurofilament light chain (sNfL), total lesion volume (TLV), and brain parenchymal fraction (BPF) were also assessed. The associations of OCT with disability were examined in linear regression models with correction for age, vision, and education. RESULTS: In patients, pRNFL was associated with the Symbol Digit Modalities Test (SDMT; p = 0.030). In the multivariate analysis including sNfL and MRI measures, pRNFL (ß = 0.19, p = 0.044) and TLV (ß = -0.24, p = 0.023) were the only markers associated with the SDMT. pRNFL (p < 0.001) and GCIPL (p < 0.001) showed associations with the Expanded Disability Status Scale (EDSS). In the multivariate analysis, GCIPL showed the strongest association with the EDSS (ß = -0.32, p < 0.001) followed by sNfL (ß = 0.18, p = 0.024). CONCLUSION: The associations of OCT measures with cognitive and physical disability were independent of serum and brain MRI markers of neuroaxonal loss. OCT can be an important tool for stratification in MS, while longitudinal studies using combinations of biomarkers are warranted.

Detecting isolated cognitive relapses in persons with MS.

BACKGROUND: The existence of isolated cognitive relapses (ICRs) in persons with MS (PwMS) has been debated. OBJECTIVE: To examine relapses with decline on Symbol Digit Modalities Test (SDMT) but no change on Expanded Disability Status Scale (EDSS). METHODS: This 3-year prospective cohort study identified PwMS experiencing a relapse with decrease on SDMT. Participants with SDMT decline/stable EDSS were labeled "ICR," while those with a corresponding decrease on EDSS were classified "Relapse with Cognitive Decline (RCD)." Two definitions of SDMT decline were explored: (1) ⩾ 8 points, and (2) ⩾ 4 points. Logistic regression was used to analyze the relationship between ICR and RCD. RESULTS: The full cohort had 592 participants: 83 experienced relapses; 22 (26.5%) had an SDMT decrease of ⩾ 8 points; 14 (63.6%) met ICR criteria. Logistic regression (X2(1) = 5.112, p = 0.024) using demographics and disease characteristics explained 28.4% of the variance in ICR versus RCD. Only the MS Neuropsychological Questionnaire was associated with ICR (odds ratio (OR): 8.6; 95% confidence interval (CI): 1.1-16.4) 40 relapsing participants with SDMT decrease of ⩾ 4 points were identified: 26 (65%) had a stable EDSS (ICR). Logistic regression did not find any variable predictive of ICR. CONCLUSION: This prospective study demonstrates evidence of ICR in PwMS.

Performance of the Activities and Participation component of International Classification of Functioning, Disability and Health Sleep Disorders Brief Core Set in patients with obstructive sleep apnea.

Background: Limitation of daily activities and impairment of working memory have received less attention in the clinical diagnosis and prognostic assessment of obstructive sleep apnea (OSA). In this study, the Activities and Participation component of the International Classification of Functioning, Disability and Health (ICF) Sleep Disorders Brief Core Set was evaluated for its performance in predicting impaired work ability in OSA patients. Methods: A total of 221 subjects were recruited into this cross-sectional study. ICF Sleep Disorders Brief Core Set, polysomnography, and neuropsychological tests were applied for data acquisition. Data analysis was performed by regression analysis and receiver operating characteristic (ROC) construction. Results: The scores for the component Activities and Participation were significantly different between the no OSA/OSA group, and were elevated as the severity of OSA increased. Scores were positively correlated with apnea-hypopnea index (AHI), trail making test (TMT), and negatively correlated with symbol digit modalities test (SDMT) correct. The component Activities and Participation performed better with the threshold of 4 in the prediction of impaired attention and work ability in severe OSA [AHI ≥30 events/h, bottom 10% of TMT part B (TMTb) scores as the diagnostic criteria], with area under the curve, sensitivity and specificity as 0.909, 71.43% and 96.72%, respectively. Conclusions: The Activities and Participation component of the ICF Sleep Disorders Brief Core Set could have the potential to predict the impairment of attention and work ability in OSA patients. It provides a new perspective for the identification of OSA patients' disturbances in daily activities and improving the overall assessment level.

Current Status of Oral Disease-Modifying Treatment Effects on Cognitive Outcomes in Multiple Sclerosis: A Scoping Review.

INTRODUCTION: Cognitive impairment represents one of the most hidden and disabling clinical aspects of multiple sclerosis (MS). In this regard, the major challenges are represented by the need for a comprehensive and standardised cognitive evaluation of each patient, both at disease onset and during follow-up, and by the lack of clear-cut data on the effects of treatments. In the present review, we summarize the current evidence on the effects of the available oral disease-modifying treatments (DMTs) on cognitive outcome measures. MATERIALS AND METHODS: In this systematised review, we extract all the studies that reported longitudinally acquired cognitive outcome data on oral DMTs in MS patients. RESULTS: We found 29 studies that evaluated at least one oral DMT, including observational studies, randomised controlled trials, and their extension studies. Most of the studies (n = 20) evaluated sphingosine-1-phosphate (S1P) modulators, while we found seven studies on dimethyl fumarate, six on teriflunomide, and one on cladribine. The most frequently used cognitive outcome measures were SDMT and PASAT. Most of the studies reported substantial stability or mild improvement in cognitive outcomes in a short-time follow-up (duration of most studies ≤2 years). A few studies also reported MRI measures of brain atrophy. CONCLUSION: Cognitive outcomes were evaluated only in a minority of prospective studies on oral DMTs in MS patients with variable findings. More solid and numerous data are present for the S1P modulators. A standardised cognitive evaluation remains a yet unmet need to better clarify the possible positive effect of oral DMTs on cognition.

The impact of disease modifying therapies on cognitive functions typically impaired in multiple sclerosis patients: a clinician's review.

Objective: Over the last few decades clinicians have become aware that cognitive impairment might be a major cause of disability, loss of employment and poor quality of life in patients suffering from multiple sclerosis [MS].The impact of disease modifying therapies [DMTs] on cognition is still a matter of debate. Theoretically, DMTs could exert a substantial beneficial effect by means of reducing neuroinflammation and brain atrophy, which are established correlates of cognitive dysfunction. The aim of the study was to review the evidence concerning the effect of DMTs on cognitive functions. Methods: PubMed, Scopus, and the European Committee for Treatment and Research in Multiple Sclerosis [ECTRIMS] Library were searched for articles concerning the pediatric and adult populations of patients with multiple sclerosis, including clinical trials and RWD, where psychometric results were analyzed as secondary or exploratory endpoints. Results: We reviewed a total of 44 studies that were found by our search strategy, analyzed the psychological tests that were applied, the length of the follow-up, and possible limitations. We pointed out the difficulties associated with assessing of DMTs' effects on cognitive functions, and pitfalls in cognitive tools used for evaluating of MS patients. Conclusion: There is a need to highlight this aspect of MS therapies, and to collect adequate data to make informed therapeutic decisions, to improve our understanding of MS-related cognitive dysfunction and provide new therapeutic targets.

Predicting employment deterioration with the Processing Speed Test (PST) and SDMT in multiple sclerosis.

BACKGROUND: Employment deterioration is common in people with multiple sclerosis (PwMS). Clinicians often learn of job loss after its occurrence, leaving no opportunity for preventive measures. OBJECTIVES: Identify which neuropsychological measures discriminate between healthy volunteers (HVs) and employed/disabled PwMS at baseline and predict work deterioration over 2 years. METHODS: We examined 198 PwMS with computerized tests such as the Processing Speed Test (PST) and conventional tests such as the Symbol-Digit Modalities Test (SDMT), administered at baseline. Employment was assessed via Buffalo Vocational Monitoring Survey. Univariate and regression analyses identified significant predictors of PwMS categorized as work-stable versus work-deteriorated status. RESULTS: PwMS were impaired on all baseline assessments relative to HVs (p's < 0.001). Post hoc analyses showed that employed PwMS and HVs performed similarly and better than work-disabled PwMS. At the univariate level, both PST and SDMT discriminated between work-deteriorated and work-stable PwMS (p's < 0.01). The logistic regression model accounting for all measures retained PST and the computerized Walking Speed Test. PwMS with increased negative work events had lower PST (p < 0.001), SDMT (p < 0.001), and BVMT-R (p < 0.01) scores than stable PwMS. The related regression model retained PST and BVMT-R (p < 0.001). CONCLUSION: Cognition, as measured by the PST and BVMT-R, are predictive of job deterioration in PwMS and may be a useful screening tool to identify those at high risk of unemployment.

Cognitive impairment and health-related quality of life amongst older Australians: evidence from a longitudinal investigation.

INTRODUCTION: Australia's population is steadily growing older, with older persons expected to make up over 20% of the population by 2066. Ageing is strongly associated with a significant drop in cognitive ability, ranging from mild cognitive impairment to severe cognitive impairment (dementia). This study examined the association between cognitive impairment and health-related quality of life (HRQoL) in older Australians. METHODS: Two waves of longitudinal data from the nationally representative Household, Income and Labour Dynamics in Australia (HILDA) survey were utilised, with the age cut-off for older Australians defined as above 50. The final analysis included 10,737 person-year observations from 6892 unique individuals between 2012 and 2016. This study utilised the Backwards Digit Span (BDS) test and Symbol Digit Modalities test (SDMT) to assess cognitive function. HRQoL was measured using the physical and mental component summary scores of the SF-36 Health Survey (PCS and MCS). Additionally, HRQoL was measured using health state utility values (SF-6D score). A longitudinal random-effects GLS regression model was used to analyse the association between cognitive impairment and HRQoL. RESULTS: This study found that approximately 89% of Australian adults aged 50 or older had no cognitive impairment, 10.16% had moderate cognitive impairment, and 0.72% had severe cognitive impairment. This study also found that moderate and severe cognitive impairment were both negatively associated with HRQoL. Older Australians with moderate cognitive impairment scored worse on the PCS (ß = - 1.765, SE = 0.317), MCS (ß = - 1.612, SE = 0.326), and SF-6D (ß = - 0.024, SE = 0.004) than peers without cognitive impairment given other covariates reference categories remain constant. Older adults experiencing severe cognitive had lower PCS (ß = - 3.560, SE = 1.103), and SF-6D (ß = - 0.034, SE = 0.012) scores compared to their counterparts with no cognitive impairment given other covariates reference categories remain constant. CONCLUSION: We found evidence that HRQoL is negatively associated with cognitive impairment. Our findings will be beneficial for the future cost-effectiveness intervention targeted at reducing cognitive impairment since it provides information on the disutility associated with moderate and severe cognitive impairment.

Correlation between cognitive impairment and serum phosphorylated tau181 protein in patients with preeclampsia.

Objective: To study the cognitive function status, serum phosphorylated tau181 (P-tau181) protein level, and total tau (T-tau) protein level in patients with preeclampsia (PE), pregnant healthy controls (PHCs), and non-pregnant healthy controls (NPHCs), and to research their feasibility as serum biomarkers for evaluating cognitive functional impairment in PE patients. Methods: Sixty-eight patients with PE, 48 NPHCs, and 30 PHCs were included. Cognitive functional status was assessed using standardized Symbol Digit Modalities Test (SDMT) and Montreal Cognitive Assessment (MoCA) scales. Enzyme-linked immunosorbent assay (ELISA) was used to detect the level of serum P-tau181 and T-tau protein. The concentration of serum P-tau181 and T-tau protein were compared by one-way analysis of variance in the three groups of subjects. The correlation between P-tau181, T-tau, and SDMT was explore by multiple linear regression analysis. The areas under the receiver operating characteristic (ROC) curves of serum P-tau181 and SDMT were calculated to predict the cognitive level of subjects. Results: PE patients significantly had lower scores on SDMT (47.97 ± 7.54) and MoCA (28.00 ± 2.00) than normotensive PHCs (30.00 ± 1.25, 54.73 ± 8.55, respectively). The significant difference was found in serum P-tau181 protein levels among the three groups [H(K) = 19.101, P < 0.001]. Serum P-tau181 was thicker in PE patients than PHCs or NPHCs (both P < 0.05). According to the ROC curve, T-tau had no statistical significance in predicting the ability of cognizance, while P-tau181 and SDMT had. The DeLong test showed that P-tau181 was better than T-tau in predicting the ability of cognizance (P < 0.05). Conclusion: The patients with PE have occurred the decline of cognitive function during pregnancy. The high level of serum P-tau181 can be used as a clinical laboratory indication for non-invasive assessment of cognitive functional impairment in PE patients.

Patient-reported outcome measurements in a selective cohort of relapsing-remitting multiple sclerosis patients: relationships with physical disability, cognitive impairment, and MRI-derived metrics.

BACKGROUND: The added value of patient-reported outcome measures (PROMs) in addition to standard clinical outcome tools in the assessment of relapsing-remitting multiple sclerosis (RRMS) patients' status is increasingly recognized. PROMs facilitate the detection of hidden aspects of MS and help to integrate the patient's subjective experience of health-related quality of life (HRQoL) status and treatment satisfaction in a holistic way. However, the relationship between PROMs and clinical and cognitive status has been scarcely investigated up to now. OBJECTIVE: To investigate the association of PROMs with physical and cognitive disability in a cohort of RRMS patients at initiation of a new disease-modifying treatment. METHODS: In this cross-sectional bicenter study, 59 consecutive RRMS patients underwent neurological examination with EDSS assessment, comprehensive cognitive tests (BVMT-R, SDMT, CVLT-II) and a set of self-reported questionnaires. Lesion and brain volumes were analyzed and processed by the automated MSmetrix® software (Icometrix®, Leuven, Belgium). Spearman's correlation coefficient was used to evaluate the association of collected variables. A cross-sectional logistic regression analysis was performed to find baseline correlates of cognitive impairment. RESULTS: Of the 59 RRMS patients (mean age 39 ± 9.8 years, 79.7% female, median EDSS 2.0), 33 (56%) had cognitive impairment. While almost all dimensions of health, explored by PROMs, were impacted in the overall sample, no significant difference was observed in patients with and without cognitive impairment. All PROMs were significantly associated with EDSS (R = 0.37-0.55; p < 0.05), except for the psychological component of MSIS-29, BDI and DEX-Q scores. No significant correlation was found between PROMs and cognitive performances. The cross-sectional logistic regression analysis included age, gender (female), education, EDSS, hippocampus and FLAIR lesion volumes as significant predictors of cognitive impairment. CONCLUSIONS: The data highlight that PROMs provide valuable information on the well-being of PwMS closely paralleling the extent of MS-related disability, as measured by the EDSS. Additional research should determine the relevance of PROMs as longitudinal outcome measures.

In-person and remote administrations of the symbol digit modalities test are interchangeable among persons with multiple sclerosis.

BACKGROUND: Remote administration of the Symbol Digit Modalities Test (SDMT) requires validation. OBJECTIVES: Examine interchangeability of remote and in-person SDMT administrations in persons with MS. METHODS: After in-person baseline administration, follow-up administration was either performed in-person (n = 72) or remotely via videoconferencing (n = 143). We examined whether raw score change from baseline to follow-up differed between in-person and remote follow-up modalities. RESULTS: SDMT raw score change did not differ between in-person and remote follow-up modalities (-0.1 ± 5.9 vs -0.2 ± 6.2, p = 0.995, d = 0.008), and correlations between baseline and follow-up were comparable across modalities (0.86 vs 0.88). CONCLUSIONS: Remote and in-person SDMT administrations appear interchangeable.

High levels of kappa free light chain synthesis predict cognitive decline in relapsing-remitting multiple sclerosis.

Background: Evolving evidence suggests that measurement of cerebrospinal fluid (CSF) kappa free light chain (KFLC) synthesis has high diagnostic sensitivity and specificity for multiple sclerosis (MS), but its prognostic ability is less investigated. The usefulness of KFLC in predicting cognitive impairment (CI) is still unknown. Methods: In a monocentric longitudinal retrospecitve cohort study, KFLC-index ([CSF KFLC/serum KFLC]/[CSF albumin/serum albumin]) measured by latex-enhanced immunonephelometry was prospectively determined as part of the diagnostic workup in patients with early relapsing-remitting MS (RRMS, n=77). The ability of KFLC-index to predict information processing speed (IPS) worsening as assessed with the symbol digit modalities test (SDMT) was investigated in univariable and multivariable models. Results: In patients with KFLC-index>100 (n=31), 11 subjects (35.5%) showed reduced SDMT scores by ≥8 points at follow-up (mean follow-up time 7.3 ± 2.6 years), compared with their baseline scores (p=0.01). Baseline KFLC-index>100 was strongly associated with a higher hazard of SDMT score reduction at follow-up (adjusted hazard ratio 10.5, 95% confidence interval 2.2-50.8, p=0.003; median time to SDMT reduction 7 years). Conclusion: Intrathecal KFLC synthesis has become an attractive diagnostic tool for MS. We show for the first time that in a real-world setting of early RRMS, KFLC-index predicted cognitive decline. Whether this predictive ability of KFLC-index also concerns other cognitive domains than IPS, warrants further investigations.