Статті в журналах: "MULTIPLE SCLEROSIS, MRI, COGNITIVE IMPAIRMENT"

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Millichap, J. Gordon. "Cognitive Impairment in Multiple Sclerosis and MRI." Pediatric Neurology Briefs 25, no. 1 (January 1, 2011): 7. http://dx.doi.org/10.15844/pedneurbriefs-25-1-9.

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Patti, F., MP Amato, M. Trojano, S. Bastianello, MR Tola, B. Goretti, L. Caniatti, et al. "Cognitive impairment and its relation with disease measures in mildly disabled patients with relapsing–remitting multiple sclerosis: baseline results from the Cognitive Impairment in Multiple Sclerosis (COGIMUS) study." Multiple Sclerosis Journal 15, no. 7 (June 19, 2009): 779–88. http://dx.doi.org/10.1177/1352458509105544.

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Background Cognitive impairment is a common symptom of multiple sclerosis (MS), but the association between cognitive impairment and magnetic resonance imaging (MRI) disease measures in patients with relapsing–remitting (RR) MS is unclear. Objectives To study the prevalence of cognitive impairment and its relation with MRI disease measures in mildly disabled patients with RRMS. Methods Patients aged 18–50 years with RRMS (McDonald criteria) and an Expanded Disability Status Scale (EDSS) score ≤4.0, who were enrolled in the Cognitive Impairment in Multiple Sclerosis (COGIMUS) study, underwent baseline standardized MRI complete neurological examination and neuropsychological testing. Results A total of 550 patients were enrolled, 327 of whom underwent MRI assessments. Cognitive impairment (impaired performance in ≥3 cognitive tests) was present in approximately 20% of all patients and in the subgroup who underwent MRI. T2 hyperintense and T1 hypointense lesion volumes were significantly higher in patients with cognitive impairment (defined as impaired performance on at least three tests of the Rao’s battery) than those without. EDSS score was also significantly higher in cognitively impaired than in cognitively preserved patients. Disease duration, depression, and years in formal education did not differ significantly between cognitively impaired and cognitively preserved patients. T2 lesion volume, performance intelligence quotient, and age were significant predictors of cognitive impairment in this population. Weak correlations were found between performance on individual cognitive tests and specific MRI measures, with T1 and T2 lesion volumes correlating with performance on most cognitive tests. Conclusions Cognitive impairment occurs in approximately one-fifth of mildly disabled patients with MS and is associated with specific MRI disease measures. Assessment of cognitive function at diagnosis could facilitate the identification of patients who may benefit from therapeutic intervention with disease-modifying therapies to prevent further lesion development.

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Portaccio, Emilio, Ermelinda De Meo, Angelo Bellinvia, and Maria Pia Amato. "Cognitive Issues in Pediatric Multiple Sclerosis." Brain Sciences 11, no. 4 (March 30, 2021): 442. http://dx.doi.org/10.3390/brainsci11040442.

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Multiple sclerosis (MS) is one of the leading causes of disability in young adults. The onset of MS during developmental age makes pediatric patients particularly susceptible to cognitive impairment, resulting from both disease-related damage and failure of age-expected brain growth. Despite different test batteries and definitions, cognitive impairment has been consistently reported in approximately one-third of pediatric patients with MS. However, the lack of a uniform definition of cognitive impairment and the adoption of different test batteries have led to divergent results in terms of cognitive domains more frequently affected across the cohorts explored. This heterogeneity has hampered large international collaborative studies. Moreover, research aimed at the identification of risk factors (e.g., demographic, clinical, and radiological features) or protective factors (e.g., cognitive reserve, leisure activities) for cognitive decline is still scanty. Mood disorders, such as depression and anxiety, can be detected in these patients alongside cognitive decline or in isolation, and can negatively affect quality of life scores as well as academic performances. By using MRI, cognitive impairment was attributed to damage to specific brain compartments as well as to abnormal network activation patterns. However, multimodal MRI studies are still needed in order to assess the contribution of each MRI metric to cognitive impairment. Importantly, longitudinal studies have recently demonstrated failure of age-expected brain growth and of white matter (WM) and gray matter (GM) maturation plays a relevant role in determining cognitive dysfunction, in addition to MS-related direct damage. Whether these growth retardations might result in specific cognitive profiles according to the age at disease onset has not been studied, yet. A better characterization of cognitive profiles in pediatric MS patients, as well as the definition of neuroanatomical substrates of cognitive impairment and their longitudinal evolution are needed to develop efficient therapeutic strategies against cognitive impairment in this patient population.

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Campbell, Jamie, Mara Cercignani, Dawn Langdon, and Waqar Rashid. "COGNITIVE REHABILITATION IN MULTIPLE SCLEROSIS." Journal of Neurology, Neurosurgery & Psychiatry 86, no. 11 (October 14, 2015): e4.7-e4. http://dx.doi.org/10.1136/jnnp-2015-312379.104.

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Background/aimsTo explore the feasibility and efficacy of computerised, home-based cognitive rehabilitation in patients with multiple sclerosis using neuropsychological assessment and structural and functional MRI techniques.Materials, methods or case report38 patients with MS and evidence of cognitive impairment on the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) test battery were enrolled and randomly assigned to undergo computerised cognitive rehabilitation (n=19) for six weeks or to a control condition (n=19). All patients underwent MRI at baseline (T1) and post-intervention (T2). Changes in cortical activations were explored using an n-back fMRI paradigm.ResultsCompared to baseline, patients in the treatment group showed significant improvement in the Brief Visuospatial Memory Test at T2 (p=0.035) and exhibited altered cortical fMRI activations compared to controls.ConclusionOur preliminary data support the hypothesis that home-based, computerised cognitive rehabilitation is a feasible and effective approach to improving cognitive performance in patients with MS and may reflect underlying changes in brain activations.BICAMS is a sensitive and easy to administer tool for identifying cognitive impairment in MS in the outpatient setting. Identification of cognitive impairment may have important treatment implications in the future.

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Tench, Christopher R., and Cris S. Constantinescu. "Conventional and Quantitative Magnetic Resonance Imaging and Cognitive Impairment in Multiple Sclerosis." European Neurological Review 4, no. 2 (2009): 70. http://dx.doi.org/10.17925/enr.2009.04.02.70.

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An estimated 30–70% of patients with multiple sclerosis (MS) have some cognitive impairment. Cognitive function depends on a spectrum of faculties including information processing speed, sustained attention, recent memory and executive function. The broad definition of cognition has resulted in different assessments of function, and repeatable batteries of tests have been devised to gain an overall and repeatable view of cognition in MS. Many studies have attempted to find an association between cognitive function and MS pathology using magnetic resonance imaging (MRI). Conventional MRI has been used to show the relationship between cognitive impairment and MS lesion volume and/or brain volume (reflecting atrophy). Studies using quantitative MRI to estimate the degree of abnormality in tissue that is normal-appearing on conventional MRI have also found correlations with cognitive function. Longitudinally, cognitive decline has been found to correlate with changing MRI-detectable pathology in some studies. However, consistency between studies has been lacking, and the large number of cognitive tests available makes direct comparison of different studies difficult. Focus on specific cognitive domains may alleviate this issue in future studies.

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Langdon, Dawn. "Cognitive Impairment in Multiple Sclerosis - Recent Advances and Future Prospects." European Neurological Review 5, no. 1 (2010): 69. http://dx.doi.org/10.17925/enr.2010.05.01.69.

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Multiple sclerosis (MS) is characterised not only by physical disability but also by gradual cognitive impairment. A large proportion of patients exhibit signs of cognitive deficit that negatively affect their quality of life. Reduced processing speed is often seen with the disease and several tests have been developed to measure its severity, including the Paced Auditory Serial Addition Test (PASAT) and the Symbol Digit Modality Test (SDMT). Long-term memory function is also commonly impaired in MS and studies suggest problems in primary registration of information. Also affected are executive functions used in novel planning and problem-solving. To evaluate cognitive function, cognitive test batteries with varying effectiveness have been introduced. The correlation of cognitive performance with magnetic resonance imaging (MRI) results remains inconsistent as multiple pathologies lead to the observed impairments. Therefore, combinations of MRI data are most successful at predicting deficiencies. The efficacy of current MS treatments in terms of cognition is unclear, making their clinical evaluation a great unmet need; the same is true of universal, validated cognitive measures that can be easily administered to MS patients around the world.

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Mendes, Maria Fernanda, Alessandro Finkelsztejn, Sidney Gomes, and Yára Dadalti Fragoso. "Early and severe cognitive impairment in multiple sclerosis." Dementia & Neuropsychologia 6, no. 1 (March 2012): 48–52. http://dx.doi.org/10.1590/s1980-57642012dn06010008.

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ABSTRACT Objectives: To report on four new cases of severe cognitive impairment in the early stages of multiple sclerosis (MS) and to review data on the subject since few cases have been reported worldwide. Methods: Retrospective evaluation of medical records of patients with severe cognitive impairment within the first five years of MS diagnosis. Results on neuropsychological tests and magnetic resonance imaging (MRI) were disclosed. Results: Four patients from different Brazilian neurological departments in Brazil were evaluated, all presenting with severe cognitive dysfunction classified as rapidly developing dementia. MRI images showed severe brain atrophy and basal ganglia lesions in all patients. Conclusions: Although rare, severe cognitive impairment in MS represents an important disability and may ultimately constitute another form of the disease.

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Glanz, BI, CM Holland, SA Gauthier, EL Amunwa, Z. Liptak, MK Houtchens, RA Sperling, SJ Khoury, CRG Guttmann, and HL Weiner. "Cognitive dysfunction in patients with clinically isolated syndromes or newly diagnosed multiple sclerosis." Multiple Sclerosis Journal 13, no. 8 (July 10, 2007): 1004–10. http://dx.doi.org/10.1177/1352458507077943.

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Cognitive dysfunction is common in patients with multiple sclerosis (MS), and has been associated with MRI measures of lesion burden and atrophy. Little is known about the prevalence of cognitive impairment in patients with early MS. The associations between cognitive impairment and MRI measures of disease severity early in the disease course are also unclear. This study used a brief battery of cognitive tests to determine the prevalence and pattern of cognitive impairment in patients with clinically isolated syndromes or newly diagnosed MS. The associations between cognitive impairment and MRI measures of disease severity early in the disease course were also examined. Ninety-two patients with clinically isolated syndromes or the diagnosis of MS within the last 3 years participating in the CLIMB study underwent a neurologic examination, neuropsychological evaluation and MRI at 1.5T. Forty-nine percent of patients were impaired on one or more cognitive measures. There were no significant correlations between cognitive scores and MRI measures of disease severity including total T2 lesion volume, normal appearing white matter volume, grey matter volume, and brain parenchymal fraction. These findings suggest that cognitive impairment may predate the appearance of gross structural abnormalities on MRI and serve as an early marker of disease activity in MS. Multiple Sclerosis 2007; 13: 1004—1010. http://msj.sagepub.com

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Rocca, M. A., E. De Meo, and M. Filippi. "Functional MRI in investigating cognitive impairment in multiple sclerosis." Acta Neurologica Scandinavica 134 (September 2016): 39–46. http://dx.doi.org/10.1111/ane.12654.

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Rao, Stephen M. "Cognitive Function in Patients with Multiple Sclerosis: Impairment and Treatment." International Journal of MS Care 6, no. 1 (April 1, 2004): 9–22. http://dx.doi.org/10.7224/1537-2073-6.1.9.

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Cognitive impairment is common in multiple sclerosis (MS), with up to 65% of patients exhibiting some type of neuropsychological dysfunction. The cognitive domains most affected by MS are learning and memory, attention, information processing, visuospatial abilities, and executive functioning. It is difficult to detect cognitive dysfunction in patients with MS during routine neurologic examinations because conventional measures of neurologic disability are not sensitive enough to detect cognitive impairment. Furthermore, cognitive dysfunction is only weakly correlated with the type of MS, disease duration, or physical disability. However, brain imaging studies show that a relatively strong correlation exists between cognitive dysfunction and overall lesion burden and brain atrophy in MS. This paper reviews the natural history of cognitive dysfunction, areas of cognition affected, the correlation between MRI measures and cognitive dysfunction, issues related to neuropsychological assessment, and treatment of cognitive impairment with disease-modifying MS drugs.

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Messina, Silvia, and Francesco Patti. "Gray Matters in Multiple Sclerosis: Cognitive Impairment and Structural MRI." Multiple Sclerosis International 2014 (2014): 1–9. http://dx.doi.org/10.1155/2014/609694.

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Multiple sclerosis (MS) is an immune-mediated disease affecting central nervous system (CNS). Although MS is classically considered a white matter (WM) disease, the involvement of gray matter (GM) in the pathogenic process has been confirmed by pathology studies and MRI studies. Impairment of cognitive domains such as memory, mental processing speed, attention, and executive function can occur from the early stage of the disease and tends to worsen over time, despite stable physical symptoms. WM demyelination is moderately correlated with CI, suggesting that probably WM abnormalities alone cannot fully explain the extent of clinical symptoms in MS, including CI. Several MRI techniques have shown the involvement of GM in MS and the association between GM damage, physical disability, and CI. The aim of this review is to provide an overview of CI and GM damage assessed by structural brain MRI.

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Till, C., R. Ghassemi, B. Aubert-Broche, A. Kerbrat, D. L. Collins, S. Narayanan, D. L. Arnold, M. Desrocher, J. G. Sled, and B. L. Banwell. "MRI correlates of cognitive impairment in childhood-onset multiple sclerosis." Neuropsychology 25, no. 3 (2011): 319–32. http://dx.doi.org/10.1037/a0022051.

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Mesaros, S., M. A. Rocca, K. Kacar, J. Kostic, M. Copetti, T. Stosic-Opincal, P. Preziosa, et al. "Diffusion tensor MRI tractography and cognitive impairment in multiple sclerosis." Neurology 78, no. 13 (February 29, 2012): 969–75. http://dx.doi.org/10.1212/wnl.0b013e31824d5859.

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Benedict, Ralph H. B., Jared Bruce, Michael G. Dwyer, Bianca Weinstock-Guttman, Chris Tjoa, Eleonora Tavazzi, Frederick E. Munschauer, and Robert Zivadinov. "Diffusion-weighted imaging predicts cognitive impairment in multiple sclerosis." Multiple Sclerosis Journal 13, no. 6 (February 9, 2007): 722–30. http://dx.doi.org/10.1177/1352458507075592.

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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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Hulst, Hanneke E., Karin Gehring, Bernard MJ Uitdehaag, Leo H. Visser, Chris H. Polman, Frederik Barkhof, Margriet M. Sitskoorn, and Jeroen JG Geurts. "Indicators for cognitive performance and subjective cognitive complaints in multiple sclerosis: a role for advanced MRI?" Multiple Sclerosis Journal 20, no. 8 (November 25, 2013): 1131–34. http://dx.doi.org/10.1177/1352458513513969.

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Previous studies showed that advanced neuroimaging measures (functional MRI, diffusion tensor imaging) could distinguish multiple sclerosis (MS) patients with and without cognitive impairment. Are these measures indeed better indicators for cognitive impairment or subjective cognitive complaints than conventional MRI? Fifty MS patients and 29 controls were investigated. Regression analysis, including socio-demographic data, disease characteristics, psychological measures, and (advanced) neuroimaging, showed that worse cognitive performance was associated with male sex, lower education, and lower gray matter volume. Subjective cognitive complaints were associated with fatigue and less hippocampal atrophy. Advanced MRI measures did not add to the predictive power of our model.

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Tur, C., S. Penny, Z. Khaleeli, DR Altmann, L. Cipolotti, M. Ron, AJ Thompson, and O. Ciccarelli. "Grey matter damage and overall cognitive impairment in primary progressive multiple sclerosis." Multiple Sclerosis Journal 17, no. 11 (July 29, 2011): 1324–32. http://dx.doi.org/10.1177/1352458511410341.

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Objectives: To identify associations between cognitive impairment and imaging measures in a cross-sectional study of patients with primary progressive multiple sclerosis (PPMS). Methods: Neuropsychological tests were administered to 27 patients with PPMS and 31 controls. Patients underwent brain conventional magnetic resonance imaging (MRI) sequences, volumetric scans and magnetization transfer (MT) imaging; MT ratio (MTR) parameters, grey matter (GM) and normal-appearing white matter (NAWM) volumes, and WM T2 lesion load (T2LL) were obtained. In patients, multiple linear regression models identified the imaging measure associated with the abnormal cognitive tests independently from the other imaging variables. Partial correlation coefficients (PCC) were reported. Results: Patients performed worse on tests of attention/speed of visual information processing, delayed verbal memory, and executive function, and had a worse overall cognitive performance index, when compared with controls. In patients, a lower GM peak location MTR was associated with worse overall cognitive performance ( p < 0.001, PCC = 0.77). GM mean and peak height MTR showed the strongest association with the estimated verbal intelligence quotient (IQ) decline ( p < 0.001, PCC = -0.62), and executive function ( p < 0.001, PCC = 0.79). NAWM volume was associated with attention/speed of visual information processing ( p < 0.001, PCC = 0.74), while T2LL was associated with delayed verbal memory ( p = 0.007, PCC = -0.55). Conclusions: The finding of strong associations between GM MTR, NAWM volume and T2LL and specific cognitive impairments suggests that models that predict cognitive impairment in PPMS should include comprehensive MRI assessments of both GM and WM. However, GM MTR appears to be the main correlate of overall cognitive dysfunction, underlining the role of abnormal GM integrity in determining cognitive impairment in PPMS.

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Pravatà, Emanuele, Maria A. Rocca, Paola Valsasina, Gianna C. Riccitelli, Claudio Gobbi, Giancarlo Comi, Andrea Falini, and Massimo Filippi. "Gray matter trophism, cognitive impairment, and depression in patients with multiple sclerosis." Multiple Sclerosis Journal 23, no. 14 (February 7, 2017): 1864–74. http://dx.doi.org/10.1177/1352458517692886.

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Background: Cognitive impairment and depression frequently affects patients with multiple sclerosis (MS). However, the relationship between the occurrence of depression and cognitive impairment and the development of cortical atrophy has not been fully elucidated yet. Objectives: To investigate the association of cortical and deep gray matter (GM) volume with depression and cognitive impairment in MS. Methods: Three-dimensional (3D) T1-weighted scans were obtained from 126 MS patients and 59 matched healthy controls. Cognitive impairment was assessed using the Brief Repeatable Battery of Neuropsychological Tests and depression with the Montgomery-Asberg Depression Rating Scale (MADRS). Using FreeSurfer and FIRST software, we assessed cortical thickness (CTh) and deep GM volumetry. Magnetic resonance imaging (MRI) variables explaining depression and cognitive impairment were investigated using factorial and classification analysis. Multivariate regression models correlated GM abnormalities with symptoms severity. Results: Compared with controls, MS patients exhibited widespread bilateral cortical thinning involving all brain lobes. Depressed MS showed selective CTh decrease in fronto-temporal regions, whereas cognitive impairment MS exhibited widespread fronto-parietal cortical and subcortical GM atrophy. Frontal cortical thinning was the best predictor of depression ( C-statistic = 0.7), whereas thinning of the right precuneus and high T2 lesion volume best predicted cognitive impairment ( C-statistic = 0.8). MADRS severity correlated with right entorhinal cortex thinning, whereas cognitive impairment severity correlated with left entorhinal and thalamus atrophy. Conclusion: MS-related depression is linked to circumscribed CTh changes in areas deputed to emotional behavior, whereas cognitive impairment is correlated with cortical and subcortical GM atrophy of circuits involved in cognition.

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O’Grady, Kristin P., Adrienne N. Dula, Bailey D. Lyttle, Lindsey M. Thompson, Benjamin N. Conrad, Bailey A. Box, Lydia J. McKeithan, et al. "Glutamate-sensitive imaging and evaluation of cognitive impairment in multiple sclerosis." Multiple Sclerosis Journal 25, no. 12 (September 19, 2018): 1580–92. http://dx.doi.org/10.1177/1352458518799583.

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Background: Cognitive impairment (CI) profoundly impacts quality of life for patients with multiple sclerosis (MS). Dysfunctional regulation of glutamate in gray matter (GM) has been implicated in the pathogenesis of MS by post-mortem pathological studies and in CI by in vivo magnetic resonance spectroscopy, yet GM pathology is subtle and difficult to detect using conventional T1- and T2-weighted magnetic resonance imaging (MRI). There is a need for high-resolution, clinically accessible imaging techniques that probe molecular changes in GM. Objective: To study cortical GM pathology related to CI in MS using glutamate-sensitive chemical exchange saturation transfer (GluCEST) MRI at 7.0 Tesla (7T). Methods: A total of 20 patients with relapsing-remitting MS and 20 healthy controls underwent cognitive testing, anatomical imaging, and GluCEST imaging. Glutamate-sensitive image contrast was quantified for cortical GM, compared between cohorts, and correlated with clinical measures of CI. Results and Conclusion: Glutamate-sensitive contrast was significantly increased in the prefrontal cortex of MS patients with accumulated disability ( p < 0.05). In addition, glutamate-sensitive contrast in the prefrontal cortex was significantly correlated with symbol digit modality test ( rS = −0.814) and choice reaction time ( rS = 0.772) scores in patients ( p < 0.05), suggesting that GluCEST MRI may have utility as a marker for GM pathology and CI.

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Bagnato, Francesca, Zeena Salman, Robert Kane, Sungyoung Auh, Fredric K. Cantor, Mary Ehrmantraut, Antonio Gallo, et al. "T1 cortical hypointensities and their association with cognitive disability in multiple sclerosis." Multiple Sclerosis Journal 16, no. 10 (August 10, 2010): 1203–12. http://dx.doi.org/10.1177/1352458510377223.

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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.

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Benedict, Ralph H. B., Maria Pia Amato, John DeLuca, and Jeroen J. G. Geurts. "Cognitive impairment in multiple sclerosis: clinical management, MRI, and therapeutic avenues." Lancet Neurology 19, no. 10 (October 2020): 860–71. http://dx.doi.org/10.1016/s1474-4422(20)30277-5.

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Filippi, M., M. A. Rocca, R. H. B. Benedict, J. DeLuca, J. J. G. Geurts, S. A. R. B. Rombouts, M. Ron, and G. Comi. "The contribution of MRI in assessing cognitive impairment in multiple sclerosis." Neurology 75, no. 23 (December 6, 2010): 2121–28. http://dx.doi.org/10.1212/wnl.0b013e318200d768.

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Preziosa, Paolo, Maria A. Rocca, Elisabetta Pagani, Maria Laura Stromillo, Christian Enzinger, Antonio Gallo, Hanneke E. Hulst, et al. "Structural MRI correlates of cognitive impairment in patients with multiple sclerosis." Human Brain Mapping 37, no. 4 (February 2, 2016): 1627–44. http://dx.doi.org/10.1002/hbm.23125.

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Meijer, Kim A., Nils Muhlert, Mara Cercignani, Varun Sethi, Maria A. Ron, Alan J. Thompson, David H. Miller, Declan Chard, Jeroen JG Geurts, and Olga Ciccarelli. "White matter tract abnormalities are associated with cognitive dysfunction in secondary progressive multiple sclerosis." Multiple Sclerosis Journal 22, no. 11 (July 11, 2016): 1429–37. http://dx.doi.org/10.1177/1352458515622694.

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Background: While our knowledge of white matter (WM) pathology underlying cognitive impairment in relapsing remitting multiple sclerosis (MS) is increasing, equivalent understanding in those with secondary progressive (SP) MS lags behind. Objective: The aim of this study is to examine whether the extent and severity of WM tract damage differ between cognitively impaired (CI) and cognitively preserved (CP) secondary progressive multiple sclerosis (SPMS) patients. Methods: Conventional magnetic resonance imaging (MRI) and diffusion MRI were acquired from 30 SPMS patients and 32 healthy controls (HC). Cognitive domains commonly affected in MS patients were assessed. Linear regression was used to predict cognition. Diffusion measures were compared between groups using tract-based spatial statistics (TBSS). Results: A total of 12 patients were classified as CI, and processing speed was the most commonly affected domain. The final regression model including demographic variables and radial diffusivity explained the greatest variance of cognitive performance ( R2 = 0.48, p = 0.002). SPMS patients showed widespread loss of WM integrity throughout the WM skeleton when compared with HC. When compared with CP patients, CI patients showed more extensive and severe damage of several WM tracts, including the fornix, superior longitudinal fasciculus and forceps major. Conclusion: Loss of WM integrity assessed using TBSS helps to explain cognitive decline in SPMS patients.

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Kalb, Rosalind, Meghan Beier, Ralph HB Benedict, Leigh Charvet, Kathleen Costello, Anthony Feinstein, Jeffrey Gingold, et al. "Recommendations for cognitive screening and management in multiple sclerosis care." Multiple Sclerosis Journal 24, no. 13 (October 10, 2018): 1665–80. http://dx.doi.org/10.1177/1352458518803785.

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Purpose: To promote understanding of cognitive impairment in multiple sclerosis (MS), recommend optimal screening, monitoring, and treatment strategies, and address barriers to optimal management. Methods: The National MS Society (“Society”) convened experts in cognitive dysfunction (clinicians, researchers, and lay people with MS) to review the published literature, reach consensus on optimal strategies for screening, monitoring, and treating cognitive changes, and propose strategies to address barriers to optimal care. Recommendations: Based on current evidence, the Society makes the following recommendations, endorsed by the Consortium of Multiple Sclerosis Centers and the International Multiple Sclerosis Cognition Society: Increased professional and patient awareness/education about the prevalence, impact, and appropriate management of cognitive symptoms. For adults and children (8+ years of age) with clinical or magnetic resonance imaging (MRI) evidence of neurologic damage consistent with MS: As a minimum, early baseline screening with the Symbol Digit Modalities Test (SDMT) or similarly validated test, when the patient is clinically stable; Annual re-assessment with the same instrument, or more often as needed to (1) detect acute disease activity; (2) assess for treatment effects (e.g. starting/changing a disease-modifying therapy) or for relapse recovery; (3) evaluate progression of cognitive impairment; and/or (4) screen for new-onset cognitive problems. For adults (18+ years): more comprehensive assessment for anyone who tests positive on initial cognitive screening or demonstrates significant cognitive decline, especially if there are concerns about comorbidities or the individual is applying for disability due to cognitive impairment. For children (<18 years): neuropsychological evaluation for any unexplained change in school functioning (academic or behavioral). Remedial interventions/accommodations for adults and children to improve functioning at home, work, or school.

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Parmar, Katrin, Brenda Banwell, Nadine Akbar, and Sandra Bigi. "Imaging Pediatric Multiple Sclerosis—Challenges and Recent Advances." Neuropediatrics 49, no. 03 (February 26, 2018): 165–72. http://dx.doi.org/10.1055/s-0038-1635123.

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AbstractPediatric onset multiple sclerosis (POMS) is a rare disease with an incidence of 0.07 to 2.9/100'000 children per year. It follows a relapsing–remitting disease course and is characterized by rapid accrual of inflammatory lesions, high relapse frequency, and early cognitive impairment. Magnetic resonance imaging (MRI) plays a pivotal role in the diagnosis of POMS, and in the exclusion of other disorders mimicking POMS. Furthermore, MRI aids in disease monitoring, and in the evaluation of therapeutic efficacy in both clinical practice and clinical trials. Volumetric MRI studies, diffusion tensor imaging, resting-state, and task-based functional MRI provide deeper insight into the impact of POMS on maturing neural networks. This review article aims to highlight the importance of MRI in the care of POMS patients and to provide an overview on the different MRI techniques used in the management of POMS.

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Ozakbas, Serkan, Derya Kaya, and Egemen Idiman. "Early Onset Multiple Sclerosis Has Worse Prognosis Than Adult Onset Multiple Sclerosis Based on Cognition and Magnetic Resonance Imaging." Autoimmune Diseases 2012 (2012): 1–5. http://dx.doi.org/10.1155/2012/563989.

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Objectives. In the present study, we aimed to compare the childhood and adult onset multiple sclerosis patients prospectively in their adulthood on the basis of clinical and magnetic resonance imaging (MRI) findings and cognitive impairment, which have not been performed before.Patients and Methods. Forty-six patients in whom the disease onset occurred before 16 years of age were included in the present study. Study subjects were compared with 64 randomly included adult onset patients.Results. Mean disease duration, clinical course, and female to male ratio did not differ in the groups. Cerebellar/brainstem and spinal involvement at onset were significantly higher in EOMS than in AOMS. Difference in MSFC between baseline and at the end of the 5th year was significantly worse in EOMS population (). The most significant difference was found in Paced Auditory Serial Addition Test (PASAT) (). Differences between baseline and at the end of the 5th year on the basis of T1 hypointense lesions were significantly higher in early onset MS than in adult onset MS patients ().Conclusions. Early onset MS seems to have worse prognosis than that of adult onset MS on the basis of clinical manifestation, cognitive impairment, and MRI parameters.

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Jandric, Danka, Ilona Lipp, David Paling, David Rog, Gloria Castellazzi, Hamied Haroon, Laura Parkes, Geoff J. M. Parker, Valentina Tomassini, and Nils Muhlert. "Mechanisms of Network Changes in Cognitive Impairment in Multiple Sclerosis." Neurology 97, no. 19 (October 14, 2021): e1886-e1897. http://dx.doi.org/10.1212/wnl.0000000000012834.

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Background and ObjectivesCognitive impairment in multiple sclerosis (MS) is associated with functional connectivity abnormalities. While there have been calls to use functional connectivity measures as biomarkers, there remains to be a full understanding of why they are affected in MS. In this cross-sectional study, we tested the hypothesis that functional network regions may be susceptible to disease-related “wear and tear” and that this can be observable on co-occurring abnormalities on other magnetic resonance metrics. We tested whether functional connectivity abnormalities in cognitively impaired patients with MS co-occur with (1) overlapping, (2) local, or (3) distal changes in anatomic connectivity and cerebral blood flow abnormalities.MethodsMultimodal 3T MRI and assessment with the Brief Repeatable Battery of Neuropsychological tests were performed in 102 patients with relapsing-remitting MS and 27 healthy controls. Patients with MS were classified as cognitively impaired if they scored ≥1.5 SDs below the control mean on ≥2 tests (n = 55) or as cognitively preserved (n = 47). Functional connectivity was assessed with Independent Component Analysis and dual regression of resting-state fMRI images. Cerebral blood flow maps were estimated, and anatomic connectivity was assessed with anatomic connectivity mapping and fractional anisotropy of diffusion-weighted MRI. Changes in cerebral blood flow and anatomic connectivity were assessed within resting-state networks that showed functional connectivity abnormalities in cognitively impaired patients with MS.ResultsFunctional connectivity was significantly decreased in the anterior and posterior default mode networks and significantly increased in the right and left frontoparietal networks in cognitively impaired relative to cognitively preserved patients with MS (threshold-free cluster enhancement corrected at p ≤ 0.05, 2 sided). Networks showing functional abnormalities showed altered cerebral blood flow and anatomic connectivity locally and distally but not in overlapping locations.DiscussionWe provide the first evidence that functional connectivity abnormalities are accompanied by local cerebral blood flow and structural connectivity abnormalities but also demonstrate that these effects do not occur in exactly the same location. Our findings suggest a possibly shared pathologic mechanism for altered functional connectivity in brain networks in MS.

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Labbe, Tomas P., Cristian Montalba, Mariana Zurita, Ethel Leslie Ciampi, Juan Pablo Cruz, Macarena Vasquez, Sergio Uribe, Nicolás Crossley, and Claudia Cárcamo. "Regional brain atrophy is related to social cognition impairment in multiple sclerosis." Arquivos de Neuro-Psiquiatria 79, no. 8 (August 2021): 666–75. http://dx.doi.org/10.1590/0004-282x-anp-2020-0162.

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ABSTRACT Background: Multiple sclerosis exhibits specific neuropathological phenomena driving to both global and regional brain atrophy. At the clinical level, the disease is related to functional decline in cognitive domains as the working memory, processing speed, and verbal fluency. However, the compromise of social-cognitive abilities has concentrated some interest in recent years despite the available evidence suggesting the risk of disorganization in social life. Recent studies have used the MiniSEA test to assess the compromise of social cognition and have found relevant relationships with memory and executive functions, as well as with the level of global and regional brain atrophy. Objective: The present article aimed to identify structural changes related to socio-cognitive performance in a sample of patients with relapsing-remitting multiple sclerosis. Methods: 68 relapsing-remitting multiple sclerosis Chilean patients and 50 healthy control subjects underwent MRI scans and neuropsychological evaluation including social-cognition tasks. Total brain, white matter, and gray matter volumes were estimated. Also, voxel-based morphometry was applied to evaluate regional structural changes. Results: Patients exhibited lower scores in all neuropsychological tests. Social cognition exhibited a significant decrease in this group mostly related to the declining social perception. Normalized brain volume and white matter volume were significantly decreased when compared to healthy subjects. The regional brain atrophy analysis showed that changes in the insular cortex and medial frontal cortices are significantly related to the variability of social-cognitive performance among patients. Conclusions: In the present study, social cognition was only correlated with the deterioration of verbal fluency, despite the fact that previous studies have reported its link with memory and executive functions. The identification of specific structural correlates supports the comprehension of this phenomenon as an independent source of cognitive disability in these patients.

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Tobyne, Sean M., Wilson B. Ochoa, J. Daniel Bireley, Victoria MJ Smith, Jeroen JG Geurts, Jeremy D. Schmahmann, and Eric C. Klawiter. "Cognitive impairment and the regional distribution of cerebellar lesions in multiple sclerosis." Multiple Sclerosis Journal 24, no. 13 (September 21, 2017): 1687–95. http://dx.doi.org/10.1177/1352458517730132.

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Background: Cerebellar lesions are often reported in relapsing-remitting multiple sclerosis (RRMS) and have been associated with impaired motor function and cognitive status. However, prior research has primarily focused on summary measures of cerebellar involvement (e.g. total lesion load, gray/white matter volume) and not on the effect of lesion load within specific regions of cerebellar white matter. Objective: Spatially map the probability of cerebellar white matter lesion (CWML) occurrence in RRMS and explore the relationship between cognitive impairment and lesion (CWML) location within the cerebellum. Methods: High-resolution structural magnetic resonance imaging (MRI) was acquired on 16 cognitively impaired (CI) and 15 cognitively preserved (CP) RRMS subjects at 3T and used for lesion identification and voxel-based lesion-symptom mapping (VLSM). Results: CI RRMS demonstrated a predilection for the middle cerebellar peduncle (MCP). VLSM results indicate that lesions of the MCP are significantly associated with CI in RRMS. Measures of cerebellar lesion load were correlated with age at disease onset but not disease duration. Conclusion: A specific pattern of cerebellar lesions involving the MCP, rather than the total CWML load, contributes to cognitive dysfunction in RRMS. Cerebellar lesion profiles may provide a biomarker of current or evolving risk for cognitive status change in RRMS.

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Zivadinov, Robert. "Why Is Cognitive Impairment Present in Multiple Sclerosis? Insights from Functional MRI." Radiology 288, no. 2 (August 2018): 552–53. http://dx.doi.org/10.1148/radiol.2018180719.

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Eijlers, Anand J. C., Alle Meije Wink, Kim A. Meijer, Linda Douw, Jeroen J. G. Geurts, and Menno M. Schoonheim. "Reduced Network Dynamics on Functional MRI Signals Cognitive Impairment in Multiple Sclerosis." Radiology 292, no. 2 (August 2019): 449–57. http://dx.doi.org/10.1148/radiol.2019182623.

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Eijlers, Anand J. C., Kim A. Meijer, Thomas M. Wassenaar, Martijn D. Steenwijk, Bernard M. J. Uitdehaag, Frederik Barkhof, Alle M. Wink, Jeroen J. G. Geurts, and Menno M. Schoonheim. "Increased default-mode network centrality in cognitively impaired multiple sclerosis patients." Neurology 88, no. 10 (February 8, 2017): 952–60. http://dx.doi.org/10.1212/wnl.0000000000003689.

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Objective:To investigate how changes in functional network hierarchy determine cognitive impairment in multiple sclerosis (MS).Methods:A cohort consisting of 332 patients with MS (age 48.1 ± 11.0 years, symptom duration 14.6 ± 8.4 years) and 96 healthy controls (HCs; age 45.9 ± 10.4 years) underwent structural MRI, fMRI, and extensive neuropsychological testing. Patients were divided into 3 groups: cognitively impaired (CI; n = 87), mildly cognitively impaired (MCI; n = 65), and cognitively preserved (CP; n = 180). The functional importance of brain regions was quantified with degree centrality, the average strength of the functional connections of a brain region with the rest of the brain, and eigenvector centrality, which adds to this concept by adding additional weight to connections with brain hubs because these are known to be especially important. Centrality values were calculated for each gray matter voxel based on resting-state fMRI data, registered to standard space. Group differences were assessed with a cluster-wise permutation-based method corrected for age, sex, and education.Results:CI patients demonstrated widespread centrality increases compared to both HCs and CP patients, mainly in regions making up the default-mode network. Centrality decreases were similar in all patient groups compared to HCs, mainly in occipital and sensorimotor areas. Results were robust across centrality measures.Conclusions:Patients with MS with cognitive impairment show hallmark alterations in functional network hierarchy with increased relative importance (centrality) of the default-mode network.

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Benedict, Ralph HB, Sarah Morrow, Jonathan Rodgers, David Hojnacki, Margaret A. Bucello, Robert Zivadinov, and Bianca Weinstock-Guttman. "Characterizing cognitive function during relapse in multiple sclerosis." Multiple Sclerosis Journal 20, no. 13 (May 19, 2014): 1745–52. http://dx.doi.org/10.1177/1352458514533229.

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Objective: To characterize neuropsychological (NP) test performance during multiple sclerosis (MS) relapse and recovery. Methods: Clinical status was assessed with NP testing and Expanded Disability Status Scale (EDSS) in 24 relapsing patients, and 24 individually-matched, stable controls. All presented with cognitive symptoms as indicated by patient, clinician or caregiver perceived decline, but were free of optic neuritis, ataxia and upper extremity weakness that could compromise NP testing. The presence of enhancing magnetic resonance imaging (MRI) lesions was considered confirmatory of relapse. Relapsing patients were treated with corticosteroids. NP testing and EDSS were compared to pre-relapse baseline levels, and three-month, post-relapse, follow-up. Results: Analyses revealed significant decline on the Symbol Digit Modalities Test (SDMT) ( p=0.005) and worsening on EDSS ( p=0.019). Impairment was observed at the point of relapse in cases but not controls. The groups were no longer different at three-month follow-up. The increment of decline on SDMT was 3.5 raw score points, or roughly 6%. Conclusions: This is the first study to assess NP status changes during MS relapse using well established, reliable metrics. The presence of a clinically meaningful event is substantiated by decline in NP testing, observed or reported cognitive change, and in a subset of patients, gadolinium-enhancing MRI lesions.

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Marrie, Ruth Ann, Gordon J. Chelune, Deborah M. Miller, and Jeffrey A. Cohen. "Subjective cognitive complaints relate to mild impairment of cognition in multiple sclerosis." Multiple Sclerosis Journal 11, no. 1 (February 2005): 69–75. http://dx.doi.org/10.1191/1352458505ms1110oa.

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Cognitive impairment is common in multiple sclerosis (MS), but cannot be reliably predicted by physical impairment. The negative impact of cognitive impairment makes early detection important, but subjective cognitive complaints may be attributed to depression. We examined the relationship between subjectively reported and objectively measured cognitive impairment in MS, adjusting for mood. A neuropsychological battery, the Multiple Sclerosis Functional Composite (MSFC), the Mental Health Inventory (MHI), the Modified Fatigue Impact Scale (MFIS), the Perceived Deficits Questionnaire (PDQ) were administered to 136 patients. Demographically-adjusted cognitive scores were calculated. Subjective impairment was defined as PDQ score-2 standard deviations above that for healthy persons. We modeled the relationship of cognitive scores (independent variables) to being subjectively impaired (dependent variable) using logistic regression. Immediate Memory (IM) and Processing Speed Index (PSI) scores were non-linearly related to subjective impairment. Patients were less likely to report subjective impairment if their PSI was normal (OR-0.11; 0.02-0.73) or markedly impaired (OR-0.17; 0.03-0.91), compared to mildly reduced PSI. In young patients decreases in IM were associated with increased subjective impairment (OR-1.25; 1.07-1.47). Subjectively reported impairment reflects subtle declines in PSI and IM independent of mood, fatigue, and physical impairment. Cognitive complaints should not be discounted due to depression.

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Chamelian, Laury, Christian Bocti, Fu-Qiang Gao, Sandra E. Black, and Anthony Feinstein. "Detecting Cognitive Dysfunction in Multiple Sclerosis with a Magnetic Resonance Imaging Rating Scale: A Pilot Study." CNS Spectrums 10, no. 5 (May 2005): 394–402. http://dx.doi.org/10.1017/s1092852900022768.

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AbstractObjective: In multiple sclerosis (MS), magnetic resonance imaging (MRI) predictors of cognitive impairment are based on sophisticated computer-generated analyses that are difficult to apply in clinical settings. This study investigated the clinical usefulness of a new visual rating scale, the Cholinergic Pathways Hyperintensities Scale (CHIPS), in detecting cognitive dysfunction.Methods: Forty clinically definite MS patients underwent a brain MRI. Based on the CHIPS, cholinergic pathway hyperintensities were rated in 10 regions on four axial slices. Computerized hyperintense lesion volumes were also obtained. For cognitive testing, The Neuropsychological Screening Battery for Multiple Sclerosis was used. “Low” and “High” lesion score groups were computed based on the mean of the total CHIPS score. Optimal sensitivity and specificity of the total CHIPS score in detecting cognitive impairment were determined using a receiver operator characteristic curve.Results: Despite a similar demographic profile, subjects with a “High” lesion score performed significantly worse than the “Low” lesion score group on verbal (P=.007) and visuospatial (P=.02) memory, and on a global index of cognitive functioning (P=.001). Optimal sensitivity (82%) and specificity (83%) were reached with a threshold total CHIPS score of 18 points. Total CHIPS score and total hyperintense lesion load were correlated (σ=0.82, P<.0001).Conclusion: CHIPS is helpful in clinically predicting cognitive impairment in MS.

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Iancheva, Dessislava, Anastasiya Trenova, Stefka Mantarova, and Kiril Terziyski. "Structural and Functional MRI Techniques in Multiple Sclerosis Related Cognitive Dysfunction." Folia Medica 60, no. 4 (December 1, 2018): 505–11. http://dx.doi.org/10.2478/folmed-2018-0031.

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Abstract Multiple sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disease of the central nervous system that is prevalent in young adults and therefore with significant social impact. Cognitive impairment occurs in 40% to 70% of patients with MS and has a weak correlation with disease duration. Neuropsycho-logical assessment is a standard method in the detection of cognitive dysfunction. However, in order to understand the etiology and evolution of cognitive dysfunction, several elaborate magnetic resonance techniques have been developed. Their aim is to measure structural changes in the CNS that are considered main substrates in cognitive function such as whole brain and gray matter atrophy, cortical lesions and changes in subcortical gray matter. Evidence shows that the clinical manifestations of multiple sclerosis are complex interactions between tissue damage, tissue repair and cortical reorganization. In order to study this heterogeneity, structural magnetic resonance analysis of brain morphology and functional magnetic resonance imaging are essential. This review summarizes current techniques in structural MRI and the value of functional MRI in understanding the link between cognitive deficit and cortical activation and reorganization.

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Abou Zeid, Nuhad E., Brian G. Weinshenker, and B. Mark Keegan. "Gait Apraxia in Multiple Sclerosis." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 36, no. 5 (September 2009): 562–65. http://dx.doi.org/10.1017/s0317167100008040.

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Background:Gait apraxia is a gait disorder not attributable to motor, cerebellar, or sensory dysfunction. Gait impairment is common in Multiple Sclerosis (MS), but is mostly attributed to spasticity and ataxia. Impairment ratings scales are designed accordingly and do not separately evaluate apraxia.Objective:To describe 15 patients with gait apraxia resulting from MS as their major functional impairment.Methods:The Mayo Clinic database (1994-2007) was searched for the terms MS and gait apraxia. Inclusion criteria: Definite MS, significant gait apraxia. Exclusion criteria: alternative disorder causing apraxia, predominantly spastic/ataxic gait disorder.Results:9 (60%) of the patients were women, and 12 (80%) had a progressive MS course. Gait apraxia was evident at a median of 8 years (range 0-34) following MS onset. Median EDSS at recognition of gait apraxia was 6.5 (range 5-8). Cognitive dysfunction was present in 11 (73%) and neurogenic bladder dysfunction in 14 (93%). The commonest MRI findings were confluent periventricular T2 lesions, T1 hypointensity and generalized cerebral atrophy with symmetrical ex vacuo ventricular enlargement.Conclusion:Gait apraxia can cause significant functional impairment in MS patients, and may be underrecognized. The natural course of the neurological deficit in such patients is unknown, and may differ from that of MS patients with other ambulatory disabilities.

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Ukkonen, M., T. Vahvelainen, P. Hämäläinen, P. Dastidar, and I. Elovaara. "Cognitive dysfunction in primary progressive multiple sclerosis: a neuropsychological and MRI study." Multiple Sclerosis Journal 15, no. 9 (June 25, 2009): 1055–61. http://dx.doi.org/10.1177/1352458509106231.

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Although cognitive dysfunction is known to occur in multiple sclerosis (MS), only few studies have reported cognitive performance in patients with primary progressive MS (PPMS). To find out the pattern of cognitive performance in PPMS, 28 PPMS patients underwent an extensive battery of neuropsychological tests. The results were compared to those of healthy controls ( n = 20) and patients with secondary progressive MS (SPMS, n = 28). Furthermore, the results of neuropsychological tests in PPMS were correlated to magnetic resonance imaging findings. Our study showed that the PPMS patients have deficits in several cognitive domains when compared to age-matched and education-matched controls, but the cognitive impairment in the PPMS and SPMS patients appeared to be similar. Cognitive deficits in PPMS patients correlated with diffuse brain lesion, T1- and T2-lesion load, but no correlations were found with atrophy.

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Huiskamp, Marijn, Anand J. C. Eijlers, Tommy A. A. Broeders, Jasmin Pasteuning, Iris Dekker, Bernard M. J. Uitdehaag, Frederik Barkhof, et al. "Longitudinal Network Changes and Conversion to Cognitive Impairment in Multiple Sclerosis." Neurology 97, no. 8 (June 7, 2021): e794-e802. http://dx.doi.org/10.1212/wnl.0000000000012341.

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ObjectiveTo characterize functional network changes related to conversion to cognitive impairment in a large sample of patients with multiple sclerosis (MS) over a period of 5 years.MethodsTwo hundred twenty-seven patients with MS and 59 healthy controls of the Amsterdam MS cohort underwent neuropsychological testing and resting-state fMRI at 2 time points (time interval 4.9 ± 0.9 years). At both baseline and follow-up, patients were categorized as cognitively preserved (CP; n = 123), mildly impaired (MCI; z < −1.5 on ≥2 cognitive tests, n = 32), or impaired (CI; z < −2 on ≥2 tests, n = 72), and longitudinal conversion between groups was determined. Network function was quantified with eigenvector centrality, a measure of regional network importance, which was computed for individual resting-state networks at both time points.ResultsOver time, 18.9% of patients converted to a worse phenotype; 22 of 123 patients who were CP (17.9%) converted from CP to MCI, 10 of 123 from CP to CI (8.1%), and 12 of 32 patients with MCI converted to CI (37.5%). At baseline, default-mode network (DMN) centrality was higher in CI individuals compared to controls (p = 0.05). Longitudinally, ventral attention network (VAN) importance increased in CP, driven by stable CP and CP-to-MCI converters (p < 0.05).ConclusionsOf all patients, 19% worsened in their cognitive status over 5 years. Conversion from intact cognition to impairment is related to an initial disturbed functioning of the VAN, then shifting toward DMN dysfunction in CI. Because the VAN normally relays information to the DMN, these results could indicate that in MS normal processes crucial for maintaining overall network stability are progressively disrupted as patients clinically progress.

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Syc, Stephanie B., Daniel M. Harrison, Shiv Saidha, Michaela Seigo, Peter A. Calabresi, and Daniel S. Reich. "Quantitative MRI Demonstrates Abnormality of the Fornix and Cingulum in Multiple Sclerosis." Multiple Sclerosis International 2013 (2013): 1–9. http://dx.doi.org/10.1155/2013/838719.

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Objective. To characterize MR signal changes associated with tissue damage in the fornix and cingulum in multiple sclerosis (MS) using quantitative MRI measures and to determine associations with cognitive dysfunction.Background. The fornix and cingulum are white-matter bundles that carry information related to cognition. While cognitive dysfunction is reported in 40–60% of MS patients, the neuroanatomical correlates of cognitive impairment remain incompletely understood.Methods. The cingulum, pillars of the fornix, and corticospinal tract were segmented by fiber tracking via diffusion tensor imaging. Average tract-specific fractional anisotropy (FA), mean diffusivity (MD), and magnetization transfer ratio (MTR) were compared in MS cases and healthy volunteers. Associations with clinical measures and neuropsychological tests were derived by multivariate linear regression.Results. Fornix FA (P=0.004) and MTR (P=0.005) were decreased, and fornix MD (P<0.001) and cingulum MD (P<0.001) increased, in MS cases (n=101) relative to healthy volunteers (n=16) after adjustment for age and sex. Lower fornix FA and MTR, and higher fornix MD andλ∥, were correlated with lower PASAT-3 scores, but not with slower 25FTW times. Lower PASAT-3 scores were associated with lower cingulum FA and higher MD andλ⊥.Conclusions. Cognitive dysfunction in MS may involve damage to a widespread network of brain structures, including white-matter pathways within the limbic system.

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Brass, S. D., R. HB Benedict, B. Weinstock-Guttman, F. Munschauer, and R. Bakshi. "Cognitive impairment is associated with subcortical magnetic resonance imaging grey matter T2 hypointensity in multiple sclerosis." Multiple Sclerosis Journal 12, no. 4 (August 2006): 437–44. http://dx.doi.org/10.1191/135248506ms1301oa.

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Grey matter hypointensity on T2-weighted magnetic resonance imaging (MRI) scans, suggesting iron deposition, has been described in multiple sclerosis (MS) and is related to physical disability, disease course and brain atrophy. We tested the hypothesis that subcortical grey matter T2 hypointensity is related to cognitive impairment after adjusting for the effect of MRI lesion and atrophy measures. We studied 33 patients with MS and 14 healthy controls. Normalized T2 signal intensity in the caudate, putamen, globus pallidus and thalamus, total brain T1-hypointense lesion volume (T1LV), fluid-attenuated inversion-recovery-hyperintense lesion volume (FLLV) and brain parenchymal fraction (BPF) were obtained quantitatively. A neuropsychological composite score (NCS) encompassed new learning, attention, working memory, spatial processing and executive function. In each of the regions of interest, the normalized T2 intensity was lower in the MS versus control group (all P <0.001). Regression modelling tested the relative association between all MRI variables and NCS. Globus pallidus T2 hypointensity was the only variable selected in the final model ( R2 = 0.301, P = 0.007). Pearson correlations between MRI and NCS were T1LV: r = -0.319; FLLV: r = -0.347; BPF: r = 0.374; T2 hypointensity of the caudate: r = 0.305; globus pallidus: r = 0.395; putamen: r = 0.321; and thalamus: r = 0.265. Basal ganglia T2 hypointensity and BPF demonstrated the strongest associations with cognitive impairment on individual cognitive subtests. Subcortical grey matter T2 hypointensity is related to cognitive impairment in MS, supporting the clinical relevance of T2 hypointensity as a biological marker of MS tissue damage. These data implicate a role for basal ganglia iron deposition in neuropsychological dysfunction.

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Riccitelli, Gianna C., Elisabetta Pagani, Alessandro Meani, Paola Valsasina, Paolo Preziosa, Massimo Filippi, and Maria A. Rocca. "Cognitive impairment in benign multiple sclerosis: a multiparametric structural and functional MRI study." Journal of Neurology 267, no. 12 (July 2, 2020): 3508–17. http://dx.doi.org/10.1007/s00415-020-10025-z.

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Comi, Giancarlo, Massimo Filippi, Vittorio Martinelli, Adraina Campi, Mariaemma Rodegher, Margherita Alberoni, Graziella Sirabian, and Nicola Canal. "Brain MRI correlates of cognitive impairment in primary and secondary progressive multiple sclerosis." Journal of the Neurological Sciences 132, no. 2 (October 1995): 222–27. http://dx.doi.org/10.1016/0022-510x(95)00168-2.

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Morgen, K. "Structural and functional MRI correlates of cognitive impairment in patients with multiple sclerosis." Clinical Neurophysiology 118, no. 4 (April 2007): e76-e77. http://dx.doi.org/10.1016/j.clinph.2006.11.176.

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Yildiz, Murat, Barbara Tettenborn, Ernst-Wilhelm Radue, Kerstin Bendfeldt, and Stefan Borgwardt. "Association of cognitive impairment and lesion volumes in multiple sclerosis – A MRI study." Clinical Neurology and Neurosurgery 127 (December 2014): 54–58. http://dx.doi.org/10.1016/j.clineuro.2014.09.019.

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Benedict, Ralph HB, Hanneke E. Hulst, Niels Bergsland, Menno M. Schoonheim, Michael G. Dwyer, Bianca Weinstock-Guttman, Jeroen JG Geurts, and Robert Zivadinov. "Clinical significance of atrophy and white matter mean diffusivity within the thalamus of multiple sclerosis patients." Multiple Sclerosis Journal 19, no. 11 (March 4, 2013): 1478–84. http://dx.doi.org/10.1177/1352458513478675.

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Background: Gray-matter (GM) atrophy is strongly predictive of cognitive impairment in multiple sclerosis (MS) patients. The thalamus is the region where the atrophy/cognition correlation is most robust. However, few studies have assessed diffusion tensor imaging (DTI) metrics within the thalamus. Objective: This study was designed to determine if thalamus white matter DTI predicts cognitive impairment after accounting for the effects of volume loss. Methods: We enrolled 75 MS patients and 18 healthy controls undergoing 3T brain magnetic resonance imaging (MRI). Thalamus volumes were calculated on 3D T1 images. Voxelwise analyses of DTI metrics were performed within the thalamic white matter tracts. Neuropsychological (NP) testing, acquired using consensus standard methods, contributed measures of memory, cognitive processing speed and executive function. Results: All cognitive tests were significantly predicted ( R2 =0.31, p<0.001) by thalamus volume after accounting for influence of demographics. Mean diffusivity was retained in regression models predicting all cognitive tests, adding from 7–13% of additional explained variance ( p<0.02) after accounting for thalamus volume. Conclusions: We confirm the significant role of thalamus atrophy in MS-associated cognitive disorder, and further report that subtle thalamus pathology as detected by DTI adds incremental explained variance in predicting cognitive impairment.

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Lazeron, R. HC, D. W. Langdon, M. Filippi, J. HTM van Waesberghe, V. L. Stevenson, J. BS Boringa, D. Origgi, et al. "Neuropsychological impairment in multiple sclerosis patients: the role of (juxta)cortical lesion on FLAIR." Multiple Sclerosis Journal 6, no. 4 (August 2000): 280–85. http://dx.doi.org/10.1177/135245850000600410.

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In this study we evaluated the correlation between neuropsychological impairment (measured with the Brief Repeatable Battery Neuropsychological Tests) and (juxta)cortical lesions detected with FLAIR and the relative sensitivity of the FLAIR sequence compared to spin-echo MRI sequences in detecting (juxta)cortical MS lesions. A total of 39 patients with definite MS were evaluated by MRI with a conventional and fast spin echo sequence and fast FLAIR sequence, and neuropsychological tests of the Brief Repeatable Battery Neuropsychological tests were performed. The Z-score of all subtests were used to calculate a Cognitive Impairment Index. The results show that a high number of (juxta)cortical lesions is detected with thin slice FLAIR (30% of all lesions seen). This percentage was not superior to spin-echo, reflecting the thin slice thickness (3 mm) we used. The lesions detected with FLAIR were to a certain degree different ones than the lesions detected with the other techniques. While the number of non-cortical lesions correlated with the expanded disability status scale (r=0.32, P=0.045), the number of (juxta)cortical lesions detected with the FLAIR showed a correlation (r=0.34, P=0.035) with the Cognitive Impairment Index. Our study underlines the high number of (juxta)cortical lesions in MS and the value of thin slice FLAIR sequence to detect such lesions with MRI. It also stresses the importance of (juxta)cortical lesions on determining neuropsychological impairment.

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48

Summers, MM, LK Fisniku, VM Anderson, DH Miller, L. Cipolotti, and MA Ron. "Cognitive impairment in relapsing—remitting multiple sclerosis can be predicted by imaging performed several years earlier." Multiple Sclerosis Journal 14, no. 2 (October 17, 2007): 197–204. http://dx.doi.org/10.1177/1352458507082353.

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Cognitive deficits in multiple sclerosis (MS) are common and correlate with contemporary MRI brain abnormalities, particularly atrophy, but the ability of imaging early in the disease to predict later cognitive impairment remains to be determined. Thirty relapsing—remitting MS patients recruited within three years of the onset of the disease, and in whom MRI had been performed at baseline and a year later, were assessed neuropsychologically five years later. Imaging parameters accounting for significant variance in cognitive performance were identified using multiple regressions, once confounding variables were controlled. Patients performed significantly worse than expected on tests of attention/speed of information processing and half of them had experienced some decline in IQ in relation to premorbid estimates. The rate of global brain atrophy in the first year of the study accounted for significant variance in the overall cognitive performance, and in memory and attention/speed of information processing. Poor performance on attention tests was associated with high T1-weighted lesion volume and reduced magnetization transfer ratio (MTR) in normal-appearing white matter (NAWM). These results suggest that neuroaxonal loss was identified early in the disease, and its rate of progression, predicted cognitive impairment later in the disease. Neuroaxonal loss is likely to affect commissural and association fibres that subserve the cognitive processes impaired in MS. Multiple Sclerosis 2008; 14: 197—204. http://msj.sagepub.com

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Papadopoulou, Athina, Nicole Müller-Lenke, Yvonne Naegelin, Gabriela Kalt, Kerstin Bendfeldt, Pascal Kuster, Markus Stoecklin, et al. "Contribution of cortical and white matter lesions to cognitive impairment in multiple sclerosis." Multiple Sclerosis Journal 19, no. 10 (March 4, 2013): 1290–96. http://dx.doi.org/10.1177/1352458513475490.

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Background: Cortical lesions (CLs) have been reported to be a better predictor for cognitive impairment than white matter (WM) lesions in relapsing–remitting multiple sclerosis (RRMS). Objectives: The objectives of this article are to investigate the contribution of CLs and WM lesions to cognitive impairment in 91 patients with MS and clinically isolated syndrome, and to test potential associations of CLs and WM lesions with fatigue and depression. Methods: Lesions were scored and segmented on 3D double inversion recovery sequences, according to their location (cortical, WM). Normalised grey matter volume was also determined. Cognitive performance was assessed with the SDMT and PASAT-3, fatigue with the FSMC and depression with the German version of the CES-D. Results: CL volume did not correlate with fatigue or depression, but correlated significantly with both neuropsychological outcome measures: PASAT-3 ( r = −0.275, p = 0.009) and SDMT ( r = −0.377, p < 0.001). Multiple regression analyses with age, WM lesions, CLs and GM volume as independent variables, however, did not reveal CL volume as a significant predictor of neuropsychological outcomes, whereas WM lesion volume significantly predicted SDMT and by trend PASAT performance. Conclusions: These findings suggest a role of WM lesions in the development of cognitive deficits, especially information-processing speed, which may be higher than previously assumed. Abbreviations: CES-D: Center for Epidemiologic Studies Depression scale (ADS-L: Allgemeine Depressions Skala-L, German version of CES-D), CIS: clinically isolated syndrome, CL: cortical lesion, DIR: double inversion recovery, EDSS: Expanded Disability Status Scale, FSMC: fatigue scale for motor and cognitive functions, GM: grey matter, MRI: magnetic resonance imaging, MS: multiple sclerosis, PASAT-3: paced auditory serial addition test 3s, PPMS: primary progressive multiple sclerosis, RRMS: relapsing–remitting multiple sclerosis, SDMT: symbol digit modalities test, SPM: statistical parametric mapping, SPMS: secondary progressive multiple sclerosis, WM: white matter

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50

Damasceno, Alfredo, Luciana Ramalho Pimentel-Silva, Benito Pereira Damasceno, and Fernando Cendes. "Cognitive trajectories in relapsing–remitting multiple sclerosis: A longitudinal 6-year study." Multiple Sclerosis Journal 26, no. 13 (October 11, 2019): 1740–51. http://dx.doi.org/10.1177/1352458519878685.

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Background: Information concerning longitudinal cognitive trajectories in multiple sclerosis (MS) is relatively scarce. Moreover, it is unclear which factors are associated with cognitive decline and what is the clinical impact of cognitive impairment (CI) in the long run. Objective: To investigate cognitive trajectories in relapsing–remitting multiple sclerosis (RRMS) patients, analyzing clinical and magnetic resonance imaging (MRI) predictors of cognitive decline. Methods: We enrolled 42 patients and 30 controls. They underwent brain MRI and clinical/neuropsychological evaluation at baseline and after 1, 2, and 6 years. We evaluated cognitive domains with principal component analysis and performed multivariable regression analyzing predictors of clinical/cognitive deterioration. We also performed repeated measures analysis to assess whether clinical progression was different according to CI at baseline. Results: A total of 23 (62.2%) patients deteriorated in combined cognitive domains after 6 years, most in processing speed and memory. The number of baseline impaired cognitive domains was strongly associated with 6-year cognitive ( R2 = 0.452; p < 0.001) and Expanded Disability Status Scale (EDSS) deterioration ( R2 = 0.263; p < 0.001). Patients with baseline CI in combined domains had worse clinical progression. Conclusion: Isolated CI tends to become more widespread, affecting memory and processing speed alongside. The extent of baseline CI was the best predictor of both clinical and cognitive deterioration after 6 years.

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