المؤلفون: Tur C., Grussu F., De Angelis F., Prados F., Kanber B., Calvi A., Eshaghi A., Charalambous T., Cortese R., Chard D. T., Chataway J., Thompson A. J., Ciccarelli O., Gandini Wheeler-Kingshott C. A. M.

المساهمون: Tur, C., Grussu, F., De Angelis, F., Prados, F., Kanber, B., Calvi, A., Eshaghi, A., Charalambous, T., Cortese, R., Chard, D. T., Chataway, J., Thompson, A. J., Ciccarelli, O., Gandini Wheeler-Kingshott, C. A. M.

مصطلحات موضوعية: Anisotropy, Caudality, Lesion spatial distribution, Magnetic resonance imaging, Multiple sclerosi, SPACE-MS

الوصف: Predicting disability in progressive multiple sclerosis (MS) is extremely challenging. Although there is some evidence that the spatial distribution of white matter (WM) lesions may play a role in disability accumulation, the lack of well-established quantitative metrics that characterise these aspects of MS pathology makes it difficult to assess their relevance for clinical progression. This study introduces a novel approach, called SPACE-MS, to quantitatively characterise spatial distributional features of brain MS lesions, so that these can be assessed as predictors of disability accumulation. In SPACE-MS, the covariance matrix of the spatial positions of each patient's lesional voxels is computed and its eigenvalues extracted. These are combined to derive rotationally-invariant metrics known to be common and robust descriptors of ellipsoid shape such as anisotropy, planarity and sphericity. Additionally, SPACE-MS metrics include a neuraxis caudality index, which we defined for the whole-brain lesion mask as well as for the most caudal brain lesion. These indicate how distant from the supplementary motor cortex (along the neuraxis) the whole-brain mask or the most caudal brain lesions are. We applied SPACE-MS to data from 515 patients involved in three studies: the MS-SMART (NCT01910259) and MS-STAT1 (NCT00647348) secondary progressive MS trials, and an observational study of primary and secondary progressive MS. Patients were assessed on motor and cognitive disability scales and underwent structural brain MRI (1.5/3.0 T), at baseline and after 2 years. The MRI protocol included 3DT1-weighted (1x1x1mm3) and 2DT2-weighted (1x1x3mm3) anatomical imaging. WM lesions were semiautomatically segmented on the T2-weighted scans, deriving whole-brain lesion masks. After co-registering the masks to the T1 images, SPACE-MS metrics were calculated and analysed through a series of multiple linear regression models, which were built to assess the ability of spatial distributional metrics to explain concurrent and future ...

وصف الملف: ELETTRONICO

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/34875458; info:eu-repo/semantics/altIdentifier/wos/WOS:000731343200004; volume:33; firstpage:1; lastpage:16; numberofpages:16; journal:NEUROIMAGE. CLINICAL; http://hdl.handle.net/11365/1192000Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85120504584; https://www.sciencedirect.com/science/article/pii/S221315822100348XTest

الإتاحة: https://doi.org/10.1016/j.nicl.2021.102904Test
http://hdl.handle.net/11365/1192000Test
https://www.sciencedirect.com/science/article/pii/S221315822100348XTest

المؤلفون: Calvi A., Tur C., Chard D., Stutters J., Ciccarelli O., Cortese R., Battaglini M., Pietroboni A., De Riz M., Galimberti D., Scarpini E., De Stefano N., Prados F., Barkhof F.

المساهمون: A. Calvi, C. Tur, D. Chard, J. Stutter, O. Ciccarelli, R. Cortese, M. Battaglini, A. Pietroboni, M. De Riz, D. Galimberti, E. Scarpini, N. De Stefano, F. Prado, F. Barkhof

مصطلحات موضوعية: Black hole, Chronic active lesion, Multiple sclerosi, SEL, Volumetric MRI, Settore BIO/13 - Biologia Applicata

الوصف: Background: Slowly expanding lesions (SELs) are MRI markers of chronic active lesions in multiple sclerosis (MS). T1-hypointense black holes, and reductions in magnetization transfer ratio (MTR) are pathologically correlated with myelin and axonal loss. While all associated with progressive MS, the relationship between these lesion’s metrics and clinical outcomes in relapse-onset MS has not been widely investigated. Objectives: To explore the relationship of SELs with T1-hypointense black holes, and longitudinal T1 intensity contrast ratio and MTR, their correlation to brain volume, and their contribution to MS disability in relapse-onset patients. Methods: 135 patients with relapsing-remitting MS (RRMS) were studied with clinical assessments and brain MRI (T2/FLAIR and T1-weighted scans at 1.5/3 T) at baseline and two subsequent follow-ups; a subset of 83 patients also had MTR acquisitions. Early-onset patients were defined when the baseline disease duration was ≤ 5 years (n = 85). SELs were identified using deformation field maps from the manually segmented baseline T2 lesions and differentiated from the non-SELs. Persisting black holes (PBHs) were defined as a subset of T2 lesions with a signal below a patient-specific grey matter T1 intensity in a semi-quantitative manner. SELs, PBH counts, and brain volume were computed, and their associations were assessed through Spearman and Pearson correlation. Clusters of patients according to low (up to 2), intermediate (3 to 10), or high (more than 10) SEL counts were determined with a Gaussian generalised mixture model. Mixed-effects and logistic regression models assessed volumes, T1 and MTR within SELs, and their correlation with Expanded Disability Status Scale (EDSS) and confirmed disability progression (CDP). Results: Mean age at study onset was 35.5 years (73% female), disease duration 5.5 years and mean time to last follow-up 6.5 years (range 1 to 12.5); median baseline EDSS 1.5 (range 0 to 5.5) and a mean EDSS change of 0.31 units at final follow-up. Among ...

العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000828057500004; volume:35; firstpage:1; lastpage:9; numberofpages:9; journal:NEUROIMAGE. CLINICAL; http://hdl.handle.net/2434/943393Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85130826700

الإتاحة: https://doi.org/10.1016/j.nicl.2022.103048Test
http://hdl.handle.net/2434/943393Test

المؤلفون: Kleerekooper, I, Traber, GL, Dell'Arti, L, Chappelle, AC, Wenniger, LJMDB, Chard, D, Petzold, A, Plant, GT, Trip, SA

المصدر: Presented at: ECTRIMS 2021. The Digital Experience. 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis, Virtual. (2021)

وصف الملف: text

العلاقة: https://discovery.ucl.ac.uk/id/eprint/10139773/1/PPON_ECTRIMS_poster.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10139773Test/

الإتاحة: https://discovery.ucl.ac.uk/id/eprint/10139773/1/PPON_ECTRIMS_poster.pdfTest
https://discovery.ucl.ac.uk/id/eprint/10139773Test/

المؤلفون: Cole JH, Raffel J, Friede T, Eshaghi A, Brownlee WJ, Chard D, De Stefano Md N, Enzinger C, Pirpamer L, Filippi M, Gasperini C, Rocca MA, Rovira A, Ruggieri S, Sastre-Garriga J, Stromillo ML, Uitdehaag BMJ, Vrenken H, Barkhof F, Nicholas R, Ciccarelli O

المساهمون: Cole, Jh, Raffel, J, Friede, T, Eshaghi, A, Brownlee, Wj, Chard, D, De Stefano Md, N, Enzinger, C, Pirpamer, L, Filippi, M, Gasperini, C, Rocca, Ma, Rovira, A, Ruggieri, S, Sastre-Garriga, J, Stromillo, Ml, Uitdehaag, Bmj, Vrenken, H, Barkhof, F, Nicholas, R, Ciccarelli, O

مصطلحات موضوعية: Adolescent, Adult, Aged, Aging, Atrophy, Brain, Demyelinating Disease, Disability Evaluation, Disease Progression, Female, Human, Longitudinal Studie, Male, Middle Aged, Multiple Sclerosi, Young Adult

الوصف: Objective: During the natural course of multiple sclerosis (MS), the brain is exposed to aging as well as disease effects. Brain aging can be modeled statistically; the so-called “brain-age” paradigm. Here, we evaluated whether brain-predicted age difference (brain-PAD) was sensitive to the presence of MS, clinical progression, and future outcomes. Methods: In a longitudinal, multicenter sample of 3,565 magnetic resonance imaging (MRI) scans, in 1,204 patients with MS and clinically isolated syndrome (CIS) and 150 healthy controls (mean follow-up time: patients 3.41 years, healthy controls 1.97 years), we measured “brain-predicted age” using T1-weighted MRI. We compared brain-PAD among patients with MS and patients with CIS and healthy controls, and between disease subtypes. Relationships between brain-PAD and Expanded Disability Status Scale (EDSS) were explored. Results: Patients with MS had markedly higher brain-PAD than healthy controls (mean brain-PAD +10.3 years; 95% confidence interval [CI] = 8.5–12.1] versus 4.3 years; 95% CI = 2.1 to 6.4; p < 0.001). The highest brain-PADs were in secondary-progressive MS (+13.3 years; 95% CI = 11.3–15.3). Brain-PAD at study entry predicted time-to-disability progression (hazard ratio 1.02; 95% CI = 1.01–1.03; p < 0.001); although normalized brain volume was a stronger predictor. Greater annualized brain-PAD increases were associated with greater annualized EDSS score (r = 0.26; p < 0.001). Interpretation: The brain-age paradigm is sensitive to MS-related atrophy and clinical progression. A higher brain-PAD at baseline was associated with more rapid disability progression and the rate of change in brain-PAD related to worsening disability. Potentially, “brain-age” could be used as a prognostic biomarker in early-stage MS, to track disease progression or stratify patients for clinical trial enrollment. ANN NEUROL 2020 ANN NEUROL 2020;88:93–105.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/32285956; info:eu-repo/semantics/altIdentifier/wos/WOS:000530530100001; volume:88; issue:1; firstpage:93; lastpage:105; numberofpages:13; journal:ANNALS OF NEUROLOGY; http://hdl.handle.net/11573/1473121Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85084050634

الإتاحة: https://doi.org/10.1002/ana.25746Test
http://hdl.handle.net/11573/1473121Test

المؤلفون: Geraldes R., Jurynczyk M., dos Passos G. R., Pichler A., Chung K., Hagens M., Ruggieri S., Auger C., Sastre-Garriga J., Enzinger C., Chard D., Barkhof F., Gasperini C., Rovira A., DeLuca G., Palace J.

المساهمون: Geraldes, R., Jurynczyk, M., dos Passos, G. R., Pichler, A., Chung, K., Hagens, M., Ruggieri, S., Auger, C., Sastre-Garriga, J., Enzinger, C., Chard, D., Barkhof, F., Gasperini, C., Rovira, A., Deluca, G., Palace, J.

مصطلحات موضوعية: cerebral small vessel disease, differential diagnosi, imaging, Multiple sclerosis

الوصف: Background: Differentiating multiple sclerosis (MS) from vascular risk factor (VRF)-small vessel disease (SVD) can be challenging. Objective and Methods: In order to determine whether or not pontine lesion location is a useful discriminator of MS and VRF-SVD, we classified pontine lesions on brain magnetic resonance imaging (MRI) as central or peripheral in 93 MS cases without VRF, 108 MS patients with VRF and 43 non-MS cases with VRF. Results: MS without VRF were more likely to have peripheral pons lesions (31.2%, 29/93) than non-MS with VRF (0%, 0/43) (Exp(B) = 29.8; 95% confidence interval (CI) = (1.98, 448.3); p = 0.014) but there were no significant differences regarding central pons lesions between MS without VRF (5.4%, 5/93) and non-MS with VRF patients (16.3%, 7/43) (Exp(B) = 0.89; 95% CI = (0.2, 3.94); p = 0.87). The presence of peripheral pons lesions discriminated between MS and VRF-SVD with 100% (95% CI = (91.8, 100)) specificity. The proportion of peripheral pons lesions in MS with VRF (30.5%, 33/108) was similar to that seen in MS without VRF (31.2%, 29/93, p = 0.99). Central lesions occurred in similar frequency in MS with VRF (8.3%, 9/108) and non-MS with VRF (16.3%, 7/43, p = 0.15). Conclusion: Peripheral pons lesion location is a good discriminator of MS from vascular lesions.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/32757905; info:eu-repo/semantics/altIdentifier/wos/WOS:000556869200001; firstpage:1352458520943777; journal:MULTIPLE SCLEROSIS; http://hdl.handle.net/11573/1474624Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85089188209

الإتاحة: https://doi.org/10.1177/1352458520943777Test
http://hdl.handle.net/11573/1474624Test

المؤلفون: Almouzain, L, Stevenson, F, Chard, D, Rahman, NA, Hamilton, F

المصدر: Multiple Sclerosis Journal - Experimental, Translational and Clinical , 7 (1) (2021)

مصطلحات موضوعية: Multiple sclerosis, relapsing-remitting, substitute, switch, interferons, glatiramer acetate

الوصف: Background: The decision to have children can be complex, particularly for people with multiple sclerosis (MS). A key concern is the use of disease modifying drugs (DMDs) during pregnancy, and how continuing, stopping or switching them may affect the mother and child. In people with active MS, stopping medications puts the mother at risk of relapse and disease rebound. Objectives: Review evidence on the effect of different switching strategies in people with stable relapsing remitting MS (RRMS). Methods: We searched MEDLINE, EMBASE, EMCARE, CINAHL, SCOPUS, Cochrane Library up to March 2020. Only papers in English were included and no other limits were applied. Seven articles were included: four cohorts, two case reports and one randomized controlled trial (RCT). Results: Two strategies were found: de-escalating, which was associated with an increased risk of relapses, and switching between first line injectables, with no change in relapse rate observed. Conclusion: Evidence on the effect of switching strategy on disease course in stable RRMS patients planning for pregnancy is scarce, but when switching, current evidence suggests the risk of relapses mirrors known medication efficacy.

وصف الملف: text

العلاقة: https://discovery.ucl.ac.uk/id/eprint/10125433/1/Chard_Switching%20treatments%20in%20clinically%20stable%20relapsing%20remitting%20multiple%20sclerosis%20patients%20planning%20for%20pregnancy_VoR.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10125433Test/

الإتاحة: https://discovery.ucl.ac.uk/id/eprint/10125433/1/Chard_Switching%20treatments%20in%20clinically%20stable%20relapsing%20remitting%20multiple%20sclerosis%20patients%20planning%20for%20pregnancy_VoR.pdfTest
https://discovery.ucl.ac.uk/id/eprint/10125433Test/

المؤلفون: Schiffmann, I, Freund, M, Engels, K, Weierstall, R, Rahn, AC, Chard, D, Lukas, C, Scheiderbauer, J, Stellmann, JP, Heesen, C

المصدر: EbM und Digitale Transformation in der Medizin; 20. Jahrestagung des Deutschen Netzwerks Evidenzbasierte Medizin; 20190321-20190323; Berlin; DOC19ebmP-EG03-06 /20190320/

مصطلحات موضوعية: ddc: 610

العلاقة: http://dx.doi.org/10.3205/19ebm061Test; http://nbn-resolving.de/urn:nbn:de:0183-19ebm0614Test; http://www.egms.de/en/meetings/ebm2019/19ebm061.shtmlTest

الإتاحة: https://doi.org/10.3205/19ebm061Test
http://nbn-resolving.de/urn:nbn:de:0183-19ebm0614Test
http://www.egms.de/en/meetings/ebm2019/19ebm061.shtmlTest

المؤلفون: Calvi, A, Haider, L, Prados, F, Tur, C, Chard, D, Barkhof, F

المصدر: Multiple Sclerosis Journal (2020) (In press).

مصطلحات موضوعية: Multiple sclerosis, chronic active lesions, imaging, magnetic resonance imaging, positron emission tomography

الوصف: New clinical activity in multiple sclerosis (MS) is often accompanied by acute inflammation which subsides. However, there is growing evidence that a substantial proportion of lesions remain active well beyond the acute phase. Chronic active lesions are most frequently found in progressive MS and are characterised by a border of inflammation associated with iron-enriched cells, leading to ongoing tissue injury. Identifying imaging markers for chronic active lesions in vivo are thus a major research goal. We reviewed the literature on imaging of chronic active lesion in MS, focussing on 'slowly expanding lesions' (SELs), detected by volumetric longitudinal magnetic resonance imaging (MRI) and 'rim-positive' lesions, identified by susceptibility iron-sensitive MRI. Both SELs and rim-positive lesions have been found to be prognostically relevant to future disability. Little is known about the co-occurrence of rims around SELs and their inter-relationship with other emerging techniques such as dynamic contrast enhancement (DCE) and positron emission tomography (PET).

وصف الملف: text

العلاقة: https://discovery.ucl.ac.uk/id/eprint/10111113/3/1352458520958589.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10111113Test/

الإتاحة: https://discovery.ucl.ac.uk/id/eprint/10111113/3/1352458520958589.pdfTest
https://discovery.ucl.ac.uk/id/eprint/10111113Test/

المؤلفون: Geraldes, R, Juryńczyk, M, Dos Passos, GR, Pichler, A, Chung, K, Hagens, M, Ruggieri, S, Auger, C, Sastre-Garriga, J, Enzinger, C, Chard, D, Barkhof, F, Gasperini, C, Rovira, A, DeLuca, G, Palace, J, MAGNIMS study group, .

المصدر: Multiple Sclerosis Journal (2020) (In press).

مصطلحات موضوعية: Multiple sclerosis, cerebral small vessel disease, differential diagnosis, imaging

الوصف: BACKGROUND: Differentiating multiple sclerosis (MS) from vascular risk factor (VRF)-small vessel disease (SVD) can be challenging. OBJECTIVE AND METHODS: In order to determine whether or not pontine lesion location is a useful discriminator of MS and VRF-SVD, we classified pontine lesions on brain magnetic resonance imaging (MRI) as central or peripheral in 93 MS cases without VRF, 108 MS patients with VRF and 43 non-MS cases with VRF. RESULTS: MS without VRF were more likely to have peripheral pons lesions (31.2%, 29/93) than non-MS with VRF (0%, 0/43) (Exp(B) = 29.8; 95% confidence interval (CI) = (1.98, 448.3); p = 0.014) but there were no significant differences regarding central pons lesions between MS without VRF (5.4%, 5/93) and non-MS with VRF patients (16.3%, 7/43) (Exp(B) = 0.89; 95% CI = (0.2, 3.94); p = 0.87). The presence of peripheral pons lesions discriminated between MS and VRF-SVD with 100% (95% CI = (91.8, 100)) specificity. The proportion of peripheral pons lesions in MS with VRF (30.5%, 33/108) was similar to that seen in MS without VRF (31.2%, 29/93, p = 0.99). Central lesions occurred in similar frequency in MS with VRF (8.3%, 9/108) and non-MS with VRF (16.3%, 7/43, p = 0.15). CONCLUSION: Peripheral pons lesion location is a good discriminator of MS from vascular lesions.

وصف الملف: text

العلاقة: https://discovery.ucl.ac.uk/id/eprint/10109508/3/Barkhof_The%20role%20of%20pontine%20lesion%20location%20in%20differentiating%20multiple%20sclerosis%20from%20vascular%20risk%20factor-related%20small%20vessel%20disease_AAM.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10109508Test/

الإتاحة: https://discovery.ucl.ac.uk/id/eprint/10109508/3/Barkhof_The%20role%20of%20pontine%20lesion%20location%20in%20differentiating%20multiple%20sclerosis%20from%20vascular%20risk%20factor-related%20small%20vessel%20disease_AAM.pdfTest
https://discovery.ucl.ac.uk/id/eprint/10109508Test/

المؤلفون: Cole, JH, Raffel, J, Friede, T, Eshaghi, A, Brownlee, WJ, Chard, D, De Stefano, N, Enzinger, C, Pirpamer, L, Filippi, M, Gasperini, C, Rocca, MA, Rovira, A, Ruggieri, S, Sastre-Garriga, J, Stromillo, ML, Uitdehaag, B, Vrenken, H, Barkhof, F, Nicholas, R, Ciccarelli, O, MAGNIMS study group

المصدر: Annals of Neurology , 88 (1) pp. 93-105. (2020)

مصطلحات موضوعية: Multiple sclerosis, brain ageing, neuroimaging

الوصف: OBJECTIVE: During the natural course of MS, the brain is exposed to ageing as well as disease effects. Brain ageing can be modelled statistically; the so-called 'brain-age' paradigm. Here, we evaluated whether brain-predicted age difference (brain-PAD) was sensitive to the presence of MS, clinical progression and future outcomes. METHODS: In a longitudinal, multi-centre sample of 3,565 MRI scans, in 1,204 MS and clinically-isolated syndrome (CIS) patients and 150 healthy controls (mean follow-up time: patients 3.41 years, healthy controls 1.97 years), we measured 'brain-predicted age' using T1-weighted MRI. We compared brain-PAD between MS and CIS patients and healthy controls, and between disease subtypes. Relationships between brain-PAD and Expanded Disability Status Scale (EDSS) were explored. RESULTS: MS patients had markedly higher brain-PAD than healthy controls (mean brain-PAD +10.3 years [95% CI 8.5, 12.1] versus 4.3 years [-2.1, 6.4], p < 0.001). The highest brain-PADs were in secondary-progressive MS (+19.4 years [17.1, 21.9]). Brain-PAD at study entry predicted time-to-disability progression (hazard ratio 1.02 [1.01, 1.03], p < 0.001); though normalised brain volume was a stronger predictor. Greater annualised brain-PAD increases were associated with greater annualised EDSS score (r = 0.26, p < 0.001). INTERPRETATION: The brain-age paradigm is sensitive to MS-related atrophy and clinical progression. A higher brain-PAD at baseline was associated with more rapid disability progression and the rate of change in brain-PAD related to worsening disability. Potentially, 'brain-age' could be used as a prognostic biomarker in early-stage MS, to track disease progression or stratify patients for clinical trial enrolment. This article is protected by copyright. All rights reserved.

وصف الملف: text

العلاقة: https://discovery.ucl.ac.uk/id/eprint/10095305/1/Barkhof_ana.25746.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10095305Test/

الإتاحة: https://discovery.ucl.ac.uk/id/eprint/10095305/1/Barkhof_ana.25746.pdfTest
https://discovery.ucl.ac.uk/id/eprint/10095305Test/