FLAIR lesion volume in multiple sclerosis: Relation to processing speed and verbal memory

Following a previous study with diffusion tensor imaging, we investigated the correlation between diffusion-weighted imaging (DWI) and cognitive dysfunction in multiple sclerosis (MS). We studied 60 MS patients (mean age 45.8±9.0 years) using 1.5-T MRI. Disease course was RR=40 and SP = 20. Mean disease duration was 12.8±8.7 years. Mean EDSS was 3.4±1.7. Whole brain, gray and white matter normalized volumes were calculated on 3D SPGR T1-WI using a fully automated Hybrid SIENAX method. Parenchymal mean diffusivity (PMD) maps were created after automated segmentation of the brain parenchyma and cerebrospinal fluid using T2-WI and DW images. Histogram analysis was performed and DWI indices of peak position (PP), peak height (PH), mean parenchymal diffusivity (MPD) and entropy were obtained. Neuropsychological (NP) evaluation emphasized auditory/verbal and visual/spatial memory, as well as processing speed and executive function. We found significant correlations between DWI and performance in all cognitive domains. Overall, stronger correlations emerged for MPD and entropy than other DWI measures, although all correlations were in the expected direction. The strongest association was between DWI entropy and performance on the Symbol Digit Modalities Test, which assesses processing speed and working memory (r = -0.54). Fisher r to z transformations revealed that DWI, gray matter (GMF) and whole brain (BPF) atrophy, T1-lesion volume (LV) and T2-LV all accounted for similar amounts of variance in NP testing. Stepwise regression models determined whether multiple MRI measures predicted unique additive variance in test performance. GMF (R2 = 0.35, F =30.82, P <0.01) and entropy (ΔR2 =0.06, ΔF=5.47, P <0.05) both accounted for unique variance in processing speed. Our data make a stronger case for the clinical validity of DWI in MS than heretofore reported. DWI has very short acquisition times, and the segmentation method applied in the present study is reliable and fully automated. Given its overall simplicity and moderate correlation with cognition, DWI may offer several logistic advantages over more traditional MRI measures when predicting the presence of NP impairment. Multiple Sclerosis 2007; 13: 722-730. http://msj.sagepub.com

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Dissociable cognitive patterns related to depression and anxiety in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458519860319 ◽

2019 ◽

Vol 26 (10) ◽

pp. 1247-1255 ◽

Cited By ~ 3

Author(s):

Victoria M Leavitt ◽

Rachel Brandstadter ◽

Michelle Fabian ◽

Ilana Katz Sand ◽

Sylvia Klineova ◽

...

Keyword(s):

Multiple Sclerosis ◽

Sex Education ◽

Processing Speed ◽

Anxiety And Depression ◽

Lesion Volume ◽

Depression And Anxiety ◽

Nonverbal Memory ◽

Cognitive Correlates ◽

Partial Correlations ◽

Mood And Cognition

Background: Individuals with multiple sclerosis (MS) frequently present with depression and anxiety, as well as cognitive impairment, challenging clinicians to disentangle interrelationships among these symptoms. Objective: To identify cognitive functions associated with anxiety and depression in MS. Methods: Mood and cognition were measured in 185 recently diagnosed patients (Reserve Against Disability in Early Multiple Sclerosis (RADIEMS) cohort), and an independent validation sample (MEM CONNECT cohort, n = 70). Partial correlations evaluated relationships of cognition to anxiety and depression controlling for age, sex, education, and premorbid verbal intelligence. Results: In RADIEMS cohort, lower anxiety was associated with better nonverbal memory ( rp = –0.220, p = 0.003) and lower depression to better attention/processing speed ( rp = –0.241, p = 0.001). Consistently, in MEM CONNECT cohort, lower anxiety was associated with better nonverbal memory ( rp = –0.271, p = 0.028) and lower depression to better attention/processing speed ( rp = –0.367, p = 0.002). Relationships were unchanged after controlling for T2 lesion volume and fatigue. Conclusion: Consistent mood–cognition relationships were identified in two independent cohorts of MS patients, suggesting that cognitive correlates of anxiety and depression are separable. This dissociation may support more precise models to inform treatment development. Treatment of mood symptoms may mitigate effects on cognition and/or treatment of cognition may mitigate effects on mood.

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Restless Legs Syndrome Severity and Cognitive Function in Adults with Multiple Sclerosis: An Exploratory Pilot Study

International Journal of MS Care ◽

10.7224/1537-2073.2020-120 ◽

2021 ◽

Author(s):

Katie L.J. Cederberg ◽

Brianna Mathison ◽

Morgan L. Schuetz ◽

Robert W. Motl

Keyword(s):

Multiple Sclerosis ◽

Cognitive Function ◽

Restless Legs Syndrome ◽

Processing Speed ◽

Verbal Memory ◽

Visual Memory ◽

Rating Scale ◽

Verbal Learning ◽

Restless Legs ◽

Falling Asleep

Abstract Background: Restless legs syndrome (RLS) is a sleep disorder present in as many as 26% of persons with multiple sclerosis (MS) and can be associated with cognitive function. The present study examined the relationships between RLS symptoms (severity, frequency, occurrence) and cognitive function in adults with MS who have RLS. Methods: Twenty-two participants attended one laboratory session and completed the International Restless Legs Syndrome Study Group Rating Scale (IRLS), the Restless Legs Syndrome-6 Scale (RLS-6), and then the Brief International Cognitive Assessment for Multiple Sclerosis battery consisting of the Symbol Digit Modalities Test; California Verbal Learning Test, Second Edition; and Brief Visuospatial Memory Test–Revised. Results: Nonparametric bivariate correlations indicated that worse IRLS total severity was associated with slower processing speed (ρ = −0.42), worse verbal memory (ρ = −0.63), and worse visual memory (ρ = −0.61); worse RLS severity at falling asleep was associated with worse verbal memory (ρ = −0.45) and worse visual memory (ρ = −0.55); and worse RLS severity during the day while active was associated with slower processing speed (ρ = −0.58), worse verbal memory (ρ = −0.52), and worse visual memory (ρ = −0.60). Conclusions: These results suggest that those with more severe RLS, including worse symptoms at falling asleep and during the day while active, might experience worse cognitive function, particularly processing speed and memory. Future research should evaluate whether treatment of RLS symptoms can offer new opportunities for managing cognitive dysfunction in adults with MS.

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Coming off cannabis: a cognitive and magnetic resonance imaging study in patients with multiple sclerosis

Brain ◽

10.1093/brain/awz213 ◽

2019 ◽

Vol 142 (9) ◽

pp. 2800-2812 ◽

Cited By ~ 7

Author(s):

Anthony Feinstein ◽

Cecilia Meza ◽

Cristiana Stefan ◽

Richard W. Staines

Keyword(s):

Multiple Sclerosis ◽

Executive Function ◽

Functional Mri ◽

Processing Speed ◽

Visual Memory ◽

Cognitive Change ◽

Group Differences ◽

Lesion Volume ◽

Memory Processing ◽

Cognitive Improvement

AbstractCognitive dysfunction affects 40–80% of patients with multiple sclerosis. Smoking cannabis may add to these deficits. It is unclear whether coming off cannabis results in cognitive improvement. To address this question, 40 patients with multiple sclerosis who started using cannabis after the onset of multiple sclerosis and who used it for at least 4 days a week over many years were divided by odd-even number selection into two groups: cannabis continuation and cannabis withdrawal. Assessments took place at baseline and after 28 days and included serial versions of the Brief Repeatable Neuropsychological Battery for multiple sclerosis containing tests of verbal and visual memory, processing speed and executive function; structural and functional MRI, the latter entailing a compatible version of the Symbol Digit Modalities Test; urine for cannabinoid metabolites to detect compliance with abstinence. Only those participants deemed globally impaired at baseline (failure on at least two cognitive domains) were enrolled. The results revealed that the two groups were well matched demographically and neurologically. One subject was removed from the withdrawal group because of failed abstinence. Urine analysis revealed the cannabinoid consumed was predominantly tetrahydrocannabinol (THC). There were no baseline between group cognitive differences, but by Day 28 the withdrawal group performed significantly better on every cognitive index (P < 0.0001 for all). Significant within group differences were present for every test over time, but only in the abstinent group (P < 0.0001 for all tests). There were no between group baseline or Day 28 differences in structural MRI indices (global atrophy, total T1 and T2 lesion volume). At index assessment the two groups had a similar performance on the functional MRI-compatible Symbol Digit Modalities Test and there were no group differences in brain activation. However, by Day 28, the withdrawal group completed more trials correctly (P < 0.012) and had a faster reaction time (P < 0.002), associated with significantly increased activation in brain regions known to be associated with performance of the test (bilateral inferior frontal gyri, caudate and declive/cerebellum, P < 0.001 for all regions). These results reveal that patients with multiple sclerosis who are frequent, long-term cannabis users can show significant improvements in memory, processing speed and executive function after 28 days of drug abstinence. The absence of similar improvements in a matched multiple sclerosis group that remained on cannabis shows that beneficial cognitive change after stopping cannabis is not solely attributable to the effects of practice.

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Whole Brain Tract Disruption Better Explains Cognitive Decline in Multiple Sclerosis than Total Lesion Volume

10.26226/morressier.59a3e8b7d462b8028d895711 ◽

2017 ◽

Author(s):

Tom Fuchs

Keyword(s):

Multiple Sclerosis ◽

Cognitive Decline ◽

Lesion Volume ◽

Whole Brain

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Changes in Cerebrospinal Fluid Balance of TNF and TNF Receptors in Naïve Multiple Sclerosis Patients: Early Involvement in Compartmentalised Intrathecal Inflammation

Cells ◽

10.3390/cells10071712 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1712

Author(s):

Roberta Magliozzi ◽

Francesco Pezzini ◽

Mairi Pucci ◽

Stefania Rossi ◽

Francesco Facchiano ◽

...

Keyword(s):

Multiple Sclerosis ◽

Immune Cell ◽

Protein Pattern ◽

Fold Change ◽

Cortical Lesion ◽

Control Group ◽

Lesion Volume ◽

Mri Features ◽

Csf Levels ◽

Multiple Sclerosis Patients

An imbalance of TNF signalling in the inflammatory milieu generated by meningeal immune cell infiltrates in the subarachnoid space in multiple sclerosis (MS), and its animal model may lead to increased cortical pathology. In order to explore whether this feature may be present from the early stages of MS and may be associated with the clinical outcome, the protein levels of TNF, sTNF-R1 and sTNF-R2 were assayed in CSF collected from 122 treatment-naïve MS patients and 36 subjects with other neurological conditions at diagnosis. Potential correlations with other CSF cytokines/chemokines and with clinical and imaging parameters at diagnosis (T0) and after 2 years of follow-up (T24) were evaluated. Significantly increased levels of TNF (fold change: 7.739; p < 0.001), sTNF-R1 (fold change: 1.693; p < 0.001) and sTNF-R2 (fold change: 2.189; p < 0.001) were detected in CSF of MS patients compared to the control group at T0. Increased TNF levels in CSF were significantly (p < 0.01) associated with increased EDSS change (r = 0.43), relapses (r = 0.48) and the appearance of white matter lesions (r = 0.49). CSF levels of TNFR1 were associated with cortical lesion volume (r = 0.41) at T0, as well as with new cortical lesions (r = 0.56), whilst no correlation could be found between TNFR2 levels in CSF and clinical or MRI features. Combined correlation and pathway analysis (ingenuity) of the CSF protein pattern associated with TNF expression (encompassing elevated levels of BAFF, IFN-γ, IL-1β, IL-10, IL-8, IL-16, CCL21, haptoglobin and fibrinogen) showed a particular relationship to the interaction between innate and adaptive immune response. The CSF sTNF-R1-associated pattern (encompassing high levels of CXCL13, TWEAK, LIGHT, IL-35, osteopontin, pentraxin-3, sCD163 and chitinase-3-L1) was mainly related to altered T cell and B cell signalling. Finally, the CSF TNFR2-associated pattern (encompassing high CSF levels of IFN-β, IFN-λ2, sIL-6Rα) was linked to Th cell differentiation and regulatory cytokine signalling. In conclusion, dysregulation of TNF and TNF-R1/2 pathways associates with specific clinical/MRI profiles and can be identified at a very early stage in MS patients, at the time of diagnosis, contributing to the prediction of the disease outcome.

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Assessment of Memory in Multiple Sclerosis Patients Using the Memory Assessment Scale

Perceptual and Motor Skills ◽

10.2466/pms.1998.86.3.987 ◽

1998 ◽

Vol 86 (3) ◽

pp. 987-998 ◽

Cited By ~ 8

Author(s):

Naomi D. Ling ◽

Michael J. Selby

Keyword(s):

Multiple Sclerosis ◽

Verbal Memory ◽

Memory Function ◽

Reliability And Validity ◽

Assessment Scale ◽

Validity Data ◽

Nonverbal Memory ◽

Memory Assessment ◽

Relapsing Remitting ◽

Multiple Sclerosis Patients

Previous assessment of memory function In multiple sclerosis patients has yielded mixed findings regarding the type and severity of memory deficits, which may be due to (1) differential selection of scales for memory assessment; (2) limited, inconsistent or weak reliability and validity data for the memory scales employed; (3) poor standardization techniques; (4) lack of theoretical foundation for the measure; and (5) limited control of confounding variables, e.g., education, age and the use of nonverbal memory tests. The purpose of the present study was to assess memory function in multiple sclerosis subjects using the verbal subtests of the Memory Assessment Scale, a relatively new measure designed to overcome many of the aforementioned problems. Participants included 57 patients diagnosed as relapsing-remitting, 47 diagnosed as chronic progressive (two generally recognized types of multiple sclerosis), and 132 contra) participants. A multivariate analysis controlling for age and verbal IQ was significant (Wilks = 5.64, p<.001). One way follow-up tests showed both groups with multiple sclerosis had significantly diminished performance across all memory variables when compared with controls, with the exception of List Clustering Acquisition. This indicated that the patients used clustering (mentally grouping similar words together) as often as controls did. These findings provide support for the presence of significant and consistent verbal memory impairment in multiple sclerosis patients and the particular importance of using psychometrically sound measures in the assessment of this population.

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Cognition in Early Relapsing-Remitting Multiple Sclerosis: Consequences May Be Relative to Working Memory

Journal of the International Neuropsychological Society ◽

10.1017/s1355617713000696 ◽

2013 ◽

Vol 19 (8) ◽

pp. 938-949 ◽

Cited By ~ 12

Author(s):

Lindsay I. Berrigan ◽

Jo-Anne LeFevre ◽

Laura M. Rees ◽

Jason Berard ◽

Mark S. Freedman ◽

...

Keyword(s):

Multiple Sclerosis ◽

Working Memory ◽

Processing Speed ◽

Cognitive Functions ◽

Group Membership ◽

Equation Modeling ◽

Mediating Role ◽

Relapsing Remitting ◽

Disease Stages

AbstractThe Relative Consequence Model proposes multiple sclerosis (MS) patients have a fundamental deficit in processing speed that compromises other cognitive functions. The present study examined the mediating role of processing speed, as well as working memory, in the MS-related effects on other cognitive functions for early relapsing-remitting patients. Seventy relapsing-remitting MS patients with disease duration not greater than 10 years and 72 controls completed tasks assessing processing speed, working memory, learning, and executive functioning. The possible mediating roles of speed and working memory in the MS-related effects on other cognitive functions were evaluated using structural equation modeling. Processing speed was not significantly related to group membership and could not have a mediating role. Working memory was related to group membership and functioned as a mediating/intervening factor. The results do not support the Relative Consequence Model in this sample and they challenge the notion that working memory impairment only emerges at later disease stages. The results do support a mediating/intervening role of working memory. These results were obtained for early relapsing-remitting MS patients and should not be generalized to the broader MS population. Instead, future research should examine the relations that exist at other disease stages. (JINS, 2013, 19, 1–12)

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