scholarly journals Disease Correlates of Rim Lesions on Quantitative Susceptibility Mapping in Multiple Sclerosis

Author(s):  
Melanie Marcille ◽  
Sandra Hurtado Rúa ◽  
Charles Tyshkov ◽  
Abhishek Jaywant ◽  
Joseph Comunale ◽  
...  

Abstract Quantitative susceptibility mapping (QSM), an imaging technique sensitive to brain iron, has been used to detect paramagnetic rims of iron-laden active microglia and macrophages in a subset of multiple sclerosis (MS) lesions, known as rim+ lesions, and are consistent with chronic active lesions. Because of their potential impact on disease progression and tissue damage, investigating the influence of rim+ lesions on disability and neurodegeneration is critical to establish the impact of these lesions on the disease course. This study aimed to explore the relationship between chronic active rim+ lesions, identified as having a hyperintense rim on QSM, and both clinical disability and imaging measures of neurodegeneration in patients with MS. The patient cohort was composed of 159 relapsing-remitting multiple sclerosis patients. The Expanded Disability Status Scale (EDSS) and Brief International Cognitive Assessment for Multiple Sclerosis, which includes both the Symbol Digit Modalities Test and California Verbal Learning Test-II, were used to assess clinical disability. Cortical thickness and thalamic volume were evaluated as imaging measures of neurodegeneration. A total of 4,469 MS lesions were identified, of which 171 QSM rim+ (3.8%) lesions were identified among 57 patients (35.8%). In a multivariate regression model, as the overall total lesion burden increased, patients with at least one rim+ lesion on QSM performed worse on both physical disability and cognitive assessments, specifically the Symbol Digit Modalities Test (p=0.010), California Verbal Learning Test-II (p=0.030), and EDSS (p=0.001). In a separate univariate regression model, controlling for age (p<0.001), having at least one rim+ lesion was related to more cortical thinning (p= 0.03) in younger patients (< 45 years). Lower thalamic volume was associated with older patients (p=0.038) and larger total lesion burden (p<0.001); however, the association did not remain significant with rim+ lesions (p=0.10). Our findings demonstrate a novel observation that chronic active lesions, as identified on QSM, modify the impact of lesion burden on clinical disability in MS patients. These results support further exploration of rim+ lesions for therapeutic targeting in MS to reduce disability and subsequent neurodegeneration.

2021 ◽  
Author(s):  
Melanie Marcille ◽  
Sandra Hurtado Rua ◽  
Charles Tyshkov ◽  
Abhishek Jaywant ◽  
Joseph Comunale ◽  
...  

Objective: This study aimed to explore the association between chronic active rim+ lesions, identified as having a hyperintense rim on quantitative susceptibility mapping (QSM), on both clinical disability and imaging measures of neurodegeneration in patients with multiple sclerosis. Methods: The patient cohort was composed of 159 relapsing remitting multiple sclerosis patients aged 42.17 +/- 10.25 years and disease duration of 10.74 +/- 7.51 years. The Brief International Cognitive Assessment for Multiple Sclerosis and Expanded Disability Status Scale (EDSS) were used to assess clinical disability. Cortical thickness and thalamic volume were evaluated as imaging measures of neurodegeneration. Results: A total of 4,469 multiple sclerosis lesions were identified, of which 171 QSM rim+ (3.8%) lesions were identified among 57 patients (35.9%). In a multivariate regression model, as the overall total lesion burden increased, patients with at least one rim+ lesion on QSM performed worse on both physical disability and cognitive assessments, specifically the Symbol Digit Modalities Test (p=0.010), California Verbal Learning Test-II (p=0.030), and EDSS (p=0.001). In a separate univariate regression model, controlling for age (p<0.001), having at least one rim+ lesion was related to more cortical thinning (p= 0.03) in younger patients (< 45 years). Lower thalamic volume was associated with older patients (p=0.038) and larger total lesion burden (p<0.001) however, the association did not remain significant with rim+ lesions (p=0.10). Interpretation: Our findings demonstrate the significant impact of chronic active lesions, as identified on QSM, on both clinical disability and imaging measures of neurodegeneration in patients with multiple sclerosis.


2010 ◽  
Vol 16 (6) ◽  
pp. 715-723 ◽  
Author(s):  
JF Lovera ◽  
E. Frohman ◽  
TR Brown ◽  
D. Bandari ◽  
L. Nguyen ◽  
...  

Background: Memantine, an NMDA antagonist, is effective for moderate to severe Alzheimer’s disease. Objective: Determine whether memantine improves cognitive performance (CP) among subjects with multiple sclerosis (MS) and cognitive impairment (CI). Methods: This double-blind, randomized, placebo-controlled trial (Clinicaltrials.gov NCT00300716) compared memantine 10 mg twice a day (4 week titration followed by 12 weeks on the highest tolerated dose) with placebo. The primary outcome was the change from baseline to exit on the Paced Auditory Serial Addition Test (PASAT) and the California Verbal Learning Test-II (CVLT-II) Long Delay Free Recall (LDFR). Secondary outcomes included additional neuropsychological tests; self-report measures of quality of life, fatigue, and depression; and family/caregiver reports of subjects’ CI and neuropsychiatric symptoms. Results: The differences between the groups on the change on the PASAT (placebo—memantine = 0.0 correct responses, 95% CI 3.4, 3.4; p = 0.9) and on CVLT-II LDFR (placebo—memantine =—0.6 words, 95% CI —2.1, 0.8; p = 0.4) as well as on the other cognitive tests were not significant. Subjects on memantine had no serious adverse events (AEs) but had more fatigue and neurological AEs as well as, per family members’ reports, less cognitive improvement and greater neuropsychiatric symptoms than subjects on placebo. Conclusion: Memantine 10 mg twice a day does not improve CP in subjects with MS, ages 18—65, without major depression, who have subjective cognitive complaints and perform worse than one SD below the mean on the PASAT or on the California Verbal Learning Test-II (total recall or delayed free recall).


2010 ◽  
Vol 16 (10) ◽  
pp. 1203-1212 ◽  
Author(s):  
Francesca Bagnato ◽  
Zeena Salman ◽  
Robert Kane ◽  
Sungyoung Auh ◽  
Fredric K Cantor ◽  
...  

Background: Neocortical lesions (NLs) largely contribute to the pathology of multiple sclerosis (MS), although their relevance in patients’ disability remains unknown. Objective: To assess the incidence of T1 hypointense NLs by 3.0-Tesla magnetic resonance imaging (MRI) in patients with MS and examine neocortical lesion association with cognitive impairment. Methods: In this case-control study, 21 MS patients and 21 age-, sex- and years of education-matched healthy volunteers underwent: (i) a neuropsychological examination rating cognitive impairment (Minimal Assessment of Cognitive Function in MS); (ii) a 3.0-Tesla MRI inclusive of an isotropic 1.0 mm3 three-dimensional inversion prepared spoiled gradient-recalled-echo (3D-IRSPGR) image and T1- and T2-weighted images. Hypointensities on 3D-IRSPGR lying in the cortex, either entirely or partially were counted and association between NLs and cognitive impairment investigated. Results: A total of 95 NLs were observed in 14 (66.7%) patients. NL+ patients performed poorer (p = 0.020) than NLpatients only on the delayed recall component of the California Verbal Learning Test. This difference lost statistical significance when a correction for white matter lesion volume was employed. Conclusions: Although T 1 hypointense NLs may be present in a relatively high proportion of multiple sclerosis patients, the impact that they have in cognitive impairment is not independent from white matter disease.


2020 ◽  
pp. 135245852094378 ◽  
Author(s):  
François Guisset ◽  
Valentina Lolli ◽  
Céline Bugli ◽  
Gaetano Perrotta ◽  
Julie Absil ◽  
...  

Background: The central vein sign (CVS) is an imaging biomarker able to differentiate multiple sclerosis (MS) from other conditions causing similar appearance lesions on magnetic resonance imaging (MRI), including cerebral small vessel disease (CSVD). However, the impact of vascular risk factors (VRFs) for CSVD on the percentage of CVS positive (CVS+) lesions in MS has never been evaluated. Objective: To investigate the association between different VRFs and the percentage of CVS+ lesions in MS. Methods: In 50 MS patients, 3T brain MRIs (including high-resolution 3-dimensional T2*-weighted images) were analyzed for the presence of the CVS and MRI markers of CSVD. A backward stepwise regression model was used to predict the combined predictive effect of VRF (i.e. age, hypertension, diabetes, obesity, ever-smoking, and hypercholesterolemia) and MRI markers of CSVD on the CVS. Results: The median frequency of CVS+ lesions was 71% (range: 35%–100%). In univariate analysis, age ( p < 0.0001), hypertension ( p < 0.001), diabetes ( p < 0.01), obesity ( p < 0.01), smoking ( p < 0.05), and the presence of enlarged-perivascular-spaces on MRI ( p < 0.005) were all associated with a lower percentage of CVS+ lesions. The stepwise regression model showed that age and arterial hypertension were both associated with the percentage of CVS+ lesions in MS (adjusted R2 = 0.46; p < 0.0001 and p = 0.01, respectively). Conclusion: The proportion of CVS+ lesions significantly decreases in older and hypertensive MS patients. Although this study was conducted in patients with an already established MS diagnosis, the diagnostic yield of the previously proposed 35% CVS proportion-based diagnostic threshold appears to be not affected. Overall these results suggest that the presence of VRF for CSVD should be taken into account during the CVS assessment.


2020 ◽  
pp. 135245852096441
Author(s):  
Zhizheng Zhuo ◽  
Yunyun Duan ◽  
Decai Tian ◽  
Xinli Wang ◽  
Chenyang Gao ◽  
...  

Background: The impact of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) on brain structure and function is unknown. Objectives: The aim of this study was to study the multimodal brain MRI alterations in MOGAD and to investigate their clinical significance. Methods: A total of 17 MOGAD, 20 aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders (AQP4 + NMOSD), and 28 healthy controls (HC) were prospectively recruited. Voxel-wise gray matter (GM) volume, fractional anisotropy (FA), mean diffusivity (MD), and degree centrality (DC) were compared between groups. Clinical associations and differential diagnosis were determined using partial correlation and stepwise logistic regression. Results: In comparison with HC, MOGAD had GM atrophy in frontal and temporal lobe, insula, thalamus, and hippocampus, and WM fiber disruption in optic radiation and anterior/posterior corona radiata; DC decreased in cerebellum and increased in temporal lobe. Compared to AQP4 + NMOSD, MOGAD presented lower GM volume in postcentral gyrus and decreased DC in cerebellum. Hippocampus/parahippocampus atrophy associated with Expanded Disability Status Scale ( R = −0.55, p = 0.04) and California Verbal Learning Test ( R = 0.62, p = 0.031). The differentiation of MOGAD from AQP4 + NMOSD achieved an accuracy of 95% using FA in splenium of corpus callosum and DC in occipital gyrus. Conclusion: Distinct structural and functional alterations were identified in MOGAD. Hippocampus/parahippocampus atrophy associated with clinical disability and cognitive impairment.


2004 ◽  
Vol 10 (4) ◽  
pp. 482-488 ◽  
Author(s):  
JACOBUS DONDERS ◽  
MICHAEL T. MINNEMA

One hundred sixty-seven children with traumatic brain injury (TBI), selected from an 8-year series of consecutive referrals to a Midwestern rehabilitation hospital, completed the California Verbal Learning Test–Children's Version (CVLT–C) and the Wechsler Intelligence Scale for Children–Third Edition (WISC–III) within 1 year after injury. A large proactive interference (PI) effect, defined as performance on the second list that was at least 1.5 standard deviations below that on the 1st one, was statistically significantly more common in this clinical sample (21%) than in the CVLT–C standardization sample (11%). Other performance discrepancies, including retroactive interference, rapid forgetting, and retrieval problems, occurred at approximately the same rate in the clinical and standardization samples. Children with anterior cerebral lesions were about 3 times less likely to have a large PI effect than children without such lesions, but the former group performed worse on the first CVLT–C list. The impact of pediatric TBI on a wide range of CVLT–C quantitative variables was mediated by speed of information processing, as assessed by the WISC–III Processing Speed factor index. It is concluded that failure to release from PI is somewhat common, although certainly not universal, in children with TBI. Unlike with adults, anterior cerebral lesions are not associated selectively with an increased risk for PI after pediatric TBI but rather with a reduced efficiency of allocation of cognitive resources. Deficits in speed of information processing appear to be primarily responsible for the learning deficits on the CVLT–C after pediatric TBI. (JINS, 2004, 10, 482–488.)


2016 ◽  
Vol 74 (12) ◽  
pp. 974-981 ◽  
Author(s):  
Marco A. G. de Caneda ◽  
Maria Cecília A. de Vecino

ABSTRACT Multiple sclerosis (MS) may present with a cognitive impairment as disabling as the physical disabilities. Therefore, routine cognitive evaluation is pivotal. Valid and reliable neuropsychological tests are essential in follow-up and to define future therapeutic interventions. Objectives To investigate the correlation between the disabilities of MS patients and their cognitive impairment assessed by the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). Methods Forty patients with definitive diagnoses of MS were selected. The correlation coefficient (r) between the Expanded Disability Status Scale (EDSS) and the neuropsychological tests of BICAMS were calculated. Results The correlation was clinically substantial and significant with r = 0.55 (p < 0.01) in the Symbol Digit Modalities Test (SDMT), 0.54 (p < 0.01) in the Brief Visuospacial Memory Test (BVMT) and 0.40 (p < 0.05) in the California Verbal Learning Test (CVLT). Conclusion BICAMS has easy and satisfactory application and evaluation for routine visits and presents a significant correlation with the EDSS. Its use may be indicated for screening and monitoring of cognitive impairment in patients with MS.


2002 ◽  
Vol 16 (3) ◽  
pp. 290-299 ◽  
Author(s):  
Suzanne Barker-Collo ◽  
Anna Clarkson ◽  
Ainsleigh Cribb ◽  
Mary Grogan

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 895-896
Author(s):  
Alexandria Irace ◽  
Nicole Armstrong ◽  
Jennifer Deal ◽  
Alexander Chern ◽  
Luigi Ferrucci ◽  
...  

Abstract Several studies have demonstrated that age-related hearing loss (defined as &gt;25 dB pure tone average [PTA]) is longitudinally associated with worse cognition. We aimed to investigate whether subclinical hearing loss (SCHL), or imperfect hearing traditionally categorized as normal (PTA ≤25 dB), may be similarly linked to cognitive decline. Subjects included cognitively normal adults ≥50 years old in the Baltimore Longitudinal Study of Aging with PTA ≤25 dB measured between January 1991 - September 1994 who had repeated cognitive assessments from January 1991 - November 2019 (n=263). The exposure was hearing based on the better ear PTA. The outcomes were standardized test scores in the following domains: learning/memory, mental status, executive function, visuospatial ability, and language. Multivariable linear-mixed effects models with random intercepts and slopes and unstructured variance-covariance structure were used to model the association between hearing and change in cognition over time, adjusting for baseline age, sex, years of education, and race. Mean age was 68.3 years (standard deviation [SD]=8.9) and follow-up ranged from 0-27.7 years (mean=12.5, SD=7.9). A 10-dB worsening in hearing was longitudinally associated with an annual decline of 0.016 SDs (95% confidence interval [CI]: 0.0002, 0.033) in California Verbal Learning Test (CVLT) short-delayed recall, 0.019 SDs (95% CI: 0.002, 0.036) in CVLT long-delayed recall, and 0.017 SDs (95% CI: 0.006, 0.028) in letter fluency after covariate adjustment. Poorer hearing among those with SCHL was associated with steeper declines in memory and verbal fluency scores. This relationship may begin at earlier levels of hearing loss than previously recognized.


Sign in / Sign up

Export Citation Format

Share Document