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  • 1
    In: Brain, Oxford University Press (OUP), Vol. 146, No. 6 ( 2023-06-01), p. 2489-2501
    Abstract: MRI and clinical features of myelin oligodendrocyte glycoprotein (MOG)-antibody disease may overlap with those of other inflammatory demyelinating conditions posing diagnostic challenges, especially in non-acute phases and when serologic testing for MOG antibodies is unavailable or shows uncertain results. We aimed to identify MRI and clinical markers that differentiate non-acute MOG-antibody disease from aquaporin 4 (AQP4)-antibody neuromyelitis optica spectrum disorder and relapsing remitting multiple sclerosis, guiding in the identification of patients with MOG-antibody disease in clinical practice. In this cross-sectional retrospective study, data from 16 MAGNIMS centres were included. Data collection and analyses were conducted from 2019 to 2021. Inclusion criteria were: diagnosis of MOG-antibody disease; AQP4-neuromyelitis optica spectrum disorder and multiple sclerosis; brain and cord MRI at least 6 months from relapse; and Expanded Disability Status Scale (EDSS) score on the day of MRI. Brain white matter T2 lesions, T1-hypointense lesions, cortical and cord lesions were identified. Random forest models were constructed to classify patients as MOG-antibody disease/AQP4-neuromyelitis optica spectrum disorder/multiple sclerosis; a leave one out cross-validation procedure assessed the performance of the models. Based on the best discriminators between diseases, we proposed a guide to target investigations for MOG-antibody disease. One hundred and sixty-two patients with MOG-antibody disease [99 females, mean age: 41 (±14) years, median EDSS: 2 (0–7.5)], 162 with AQP4-neuromyelitis optica spectrum disorder [132 females, mean age: 51 (±14) years, median EDSS: 3.5 (0–8)] , 189 with multiple sclerosis (132 females, mean age: 40 (±10) years, median EDSS: 2 (0–8)] and 152 healthy controls (91 females) were studied. In young patients ( & lt;34 years), with low disability (EDSS & lt; 3), the absence of Dawson’s fingers, temporal lobe lesions and longitudinally extensive lesions in the cervical cord pointed towards a diagnosis of MOG-antibody disease instead of the other two diseases (accuracy: 76%, sensitivity: 81%, specificity: 84%, P & lt; 0.001). In these non-acute patients, the number of brain lesions & lt; 6 predicted MOG-antibody disease versus multiple sclerosis (accuracy: 83%, sensitivity: 82%, specificity: 83%, P & lt; 0.001). An EDSS & lt; 3 and the absence of longitudinally extensive lesions in the cervical cord predicted MOG-antibody disease versus AQP4-neuromyelitis optica spectrum disorder (accuracy: 76%, sensitivity: 89%, specificity: 62%, P & lt; 0.001). A workflow with sequential tests and supporting features is proposed to guide better identification of patients with MOG-antibody disease. Adult patients with non-acute MOG-antibody disease showed distinctive clinical and MRI features when compared to AQP4-neuromyelitis optica spectrum disorder and multiple sclerosis. A careful inspection of the morphology of brain and cord lesions together with clinical information can guide further analyses towards the diagnosis of MOG-antibody disease in clinical practice.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1474117-9
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2021
    In:  Clinical Neuroradiology Vol. 31, No. 4 ( 2021-12), p. 993-1003
    In: Clinical Neuroradiology, Springer Science and Business Media LLC, Vol. 31, No. 4 ( 2021-12), p. 993-1003
    Abstract: As conventional quantitative magnetic resonance imaging (MRI) parameters are weakly associated with cognitive impairment (CI) in early multiple sclerosis (MS), we explored microstructural white matter alterations in early MS or clinically isolated syndrome (CIS) comparing patients with or without CI. Methods Based on a preceding tract-based spatial statistics analysis (3 Tesla MRI) which contrasted 106 patients with early MS or CIS and 49 healthy controls, diffusion metrics (fractional anisotropy, FA, mean diffusivity, MD) were extracted from significant clusters using an atlas-based approach. The FA and MD were compared between patients with (Ci_P n  = 14) and without (Cp_P n  = 81) cognitive impairment in a subset of patients who underwent CI screening. Results The FA was reduced in Ci_P compared to Cp_P in the splenium of corpus callosum ( p  = 0.001), right parahippocampal cingulum ( p  = 0.002) and fornix cres./stria terminalis (0.042), left posterior corona radiata ( p  = 0.012), bilateral cerebral peduncles, medial lemniscus and in cerebellar tracts. Increased MD was detected in the splenium of corpus callosum ( p  = 0.01). The CI-related localizations overlapped only partially with MS lesions. Conclusion Microstructural white matter alterations at disease onset were detectable in Ci_P compared to Cp_P in known cognitively relevant fiber tracts, indicating the relevance of early treatment initiation in MS and CIS.
    Type of Medium: Online Resource
    ISSN: 1869-1439 , 1869-1447
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2232347-8
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  • 3
    In: Clinical Neuroradiology, Springer Science and Business Media LLC, Vol. 31, No. 1 ( 2021-03), p. 225-234
    Type of Medium: Online Resource
    ISSN: 1869-1439 , 1869-1447
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2232347-8
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  • 4
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2015
    In:  Neurology - Neuroimmunology Neuroinflammation Vol. 2, No. 3 ( 2015-06), p. e85-
    In: Neurology - Neuroimmunology Neuroinflammation, Ovid Technologies (Wolters Kluwer Health), Vol. 2, No. 3 ( 2015-06), p. e85-
    Type of Medium: Online Resource
    ISSN: 2332-7812
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
    detail.hit.zdb_id: 2767740-0
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  • 5
    In: Journal of Neurology, Springer Science and Business Media LLC, Vol. 264, No. 7 ( 2017-7), p. 1402-1412
    Type of Medium: Online Resource
    ISSN: 0340-5354 , 1432-1459
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 1421299-7
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  • 6
    In: Brain Communications, Oxford University Press (OUP), Vol. 4, No. 4 ( 2022-07-04)
    Abstract: MRI is an important diagnostic tool for evaluation of myelin content in multiple sclerosis and other CNS diseases, being especially relevant for studies investigating remyelinating pharmacotherapies. In this study, we evaluated a new synthetic MRI–based myelin estimation in methylenetetrahydrofolate reductase deficiency as a treatable primary demyelinating disorder and compared this method with established diffusion tensor imaging in both methylenetetrahydrofolate reductase deficiency patients and healthy controls. This is the first synthetic MRI–based in vivo evaluation of treatment-associated remyelination. 1.5 T synthetic MRI and 3 T diffusion MRI were obtained from three methylenetetrahydrofolate reductase deficiency patients at baseline and 6 months after therapy initiation, as well as from age-matched healthy controls (diffusion tensor imaging: n = 14, synthetic MRI: n = 9). Global and regional synthetic MRI parameters (myelin volume fraction, proton density, and relaxation rates) were compared with diffusion metrics (fractional anisotropy, mean/radial/axial diffusivity) and related to healthy controls by calculating z-scores and z-deviation maps. Whole-brain myelin (% of intracranial volume) of the index patient was reduced to 6 versus 10% in healthy controls, which recovered to a nonetheless subnormal level of 6.6% following initiation of high-dosage betaine. Radial diffusivity was higher at baseline compared with healthy controls (1.34 versus 0.79 × 10−3 mm2/s), recovering at follow-up (1.19 × 10−3 mm2/s). The index patient’s lesion volume diminished by 58% under treatment. Regional analysis within lesion area and atlas-based regions revealed lower mean myelin volume fraction (12.7Baseline/14.71Follow-up%) and relaxation rates, higher proton density, as well as lower fractional anisotropy and higher radial diffusivity (1.08 × 10−3Baseline/0.94 × 10−3Follow-up) compared with healthy controls. The highest z-scores were observed for myelin volume fraction in the posterior thalamic radiation, with greater deviation from controls at baseline and reduced deviation at follow-up. Z-deviations of diffusion metrics were less pronounced for radial and mean diffusivity than for myelin volume fraction. Z-maps for myelin volume fraction of the index patient demonstrated high deviation within and beyond lesion areas, among others in the precentral and postcentral gyrus, as well as in the cerebellum, and partial remission of these alterations at follow-up, while radial diffusivity demonstrated more widespread deviations in supra- and infratentorial regions. Concordant changes of myelin volume fraction and radial diffusivity after treatment initiation, accompanied by dramatic clinical and paraclinical improvement, indicate the consistency of the methods, while myelin volume fraction seems to characterize remyelinated regions more specifically. Synthetic MRI–based myelin volume fraction provides myelin estimation consistent with changes of diffusion metrics to monitor short-term myelin changes on individual patient level.
    Type of Medium: Online Resource
    ISSN: 2632-1297
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 3020013-1
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  • 7
    In: Journal of Neurology, Springer Science and Business Media LLC, Vol. 262, No. 2 ( 2015-2), p. 365-374
    Type of Medium: Online Resource
    ISSN: 0340-5354 , 1432-1459
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2015
    detail.hit.zdb_id: 1421299-7
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  • 8
    Online Resource
    Online Resource
    Wiley ; 2017
    In:  Journal of Neuroimaging Vol. 27, No. 3 ( 2017-05), p. 348-354
    In: Journal of Neuroimaging, Wiley, Vol. 27, No. 3 ( 2017-05), p. 348-354
    Abstract: Cerebral atrophy has been suggested to be a reliable magnetic resonance imaging (MRI) predictor of subsequent disability in all stages of multiple sclerosis (MS). However, no accepted methodology for routine clinical use exists to date. We sought an easy to apply and fast technique to evaluate cerebral ventricular volume in patients with MS with similar accuracy as a semiautomatic volumetric method. METHODS The study included 104 patients, 61 diagnosed with MS and 43 with clinically isolated syndrome. In addition, 30 healthy controls were enrolled. Physical disability was assessed with the expanded disability status scale and cognitive disability with the Multiple Sclerosis Inventory Cognition (MUSIC) test. All subjects received standardized 3‐dimensional (3D) MR‐imaging on a 3 T scanner. Third ventricle volume (3VV) was obtained from 3D T1‐weighted images using a semiautomated technique, and compared against planimetric assessment of the width of the third ventricle aligned (a3VW) and unaligned (u3VW) to anatomical landmarks. RESULTS a3VW was obtained within seconds with excellent intra‐ and interrater agreement, and outperformed volumetric measurements regarding the differentiation of MS patients from healthy controls. a3VW had the strongest correlations with 3VV ( r = .78, P 〈 .001) and showed moderate inverse correlation with MUSIC cognition score ( r = −.310, P 〈 .005). CONCLUSIONS a3VW is a time‐effective and robust biomarker that has strong correlations with volumetric measurements and can be established as standard in the MRI quantification of central brain atrophy in patients with early MS.
    Type of Medium: Online Resource
    ISSN: 1051-2284 , 1552-6569
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 2035400-9
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  • 9
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Neurology - Neuroimmunology Neuroinflammation Vol. 8, No. 1 ( 2021-01), p. e906-
    In: Neurology - Neuroimmunology Neuroinflammation, Ovid Technologies (Wolters Kluwer Health), Vol. 8, No. 1 ( 2021-01), p. e906-
    Abstract: To investigate cross-sectional associations of CSF levels of neurofilament light chain (NfL) and of the newly emerging marker chitinase 3–like protein 1 (CHI3L1) with brain and spinal cord atrophy, which are established MRI markers of disease activity in MS, to study CHI3L1 and NfL in relapsing (RMS) and progressive MS (PMS), and to assess the expression of CHI3L1 in different cell types. Methods In a single-center study, 131 patients with MS (42 RMS and 89 PMS) were assessed for NfL and CHI3L1 concentrations in CSF, MRI-based spinal cord and brain volumetry, MS subtype, age, disease duration, and disability. We included 42 matched healthy controls receiving MRI. CHI3L1 expression of human brain cell types was examined in 2 published single-cell RNA sequencing data sets. Results CHI3L1 was associated with spinal cord volume (B = −1.07, 95% CI −2.04 to −0.11, p = 0.029) but not with brain volumes. NfL was associated with brain gray matter (B = −7.3, 95% CI −12.0 to −2.7, p = 0.003) but not with spinal cord volume. CHI3L1 was suitable to differentiate between progressive or relapsing MS ( p = 0.015, OR 1.0103, CI for OR 1.002–1.0187), and its gene expression was found in MS-associated microglia and macrophages and in astrocytes of MS brains. Conclusions NfL and CHI3L1 in CSF were differentially related to brain and spinal cord atrophy. CSF CHI3L1 was associated with spinal cord volume loss and was less affected than NfL by disease duration and age, whereas CSF NfL was associated with brain gray matter atrophy. CSF NfL and CHI3L1 measurement provides complementary information regarding brain and spinal cord volumes. Classification of evidence This study provides Class II evidence that CSF CHI3L1 is associated with spinal cord volume loss and that CSF NfL is associated with gray matter atrophy.
    Type of Medium: Online Resource
    ISSN: 2332-7812
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2767740-0
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  • 10
    In: European Journal of Neurology, Wiley, Vol. 30, No. 2 ( 2023-02), p. 453-462
    Abstract: Brain pseudoatrophy has been shown to play a pivotal role in the interpretation of brain atrophy measures during the first year of disease‐modifying therapy in multiple sclerosis. Whether pseudoatrophy also affects the spinal cord remains unclear. The aim of this study was to analyze the extent of pseudoatrophy in the upper spinal cord during the first 2 years after therapy initiation and compare this to the brain. Methods A total of 129 patients from a prospective longitudinal multicentric national cohort study for whom magnetic resonance imaging scans at baseline, 12 months, and 24 months were available were selected for brain and spinal cord volume quantification. Annual percentage brain volume and cord area change were calculated using SIENA (Structural Image Evaluation of Normalized Atrophy) and NeuroQLab, respectively. Linear mixed model analyses were performed to compare patients on interferon‐beta therapy ( n  = 84) and untreated patients ( n  = 45). Results Patients treated with interferon‐beta demonstrated accelerated annual percentage brain volume and cervical cord area change in the first year after treatment initiation, whereas atrophy rates stabilized to a similar and not significantly different level compared to untreated patients during the second year. Conclusions These results suggest that pseudoatrophy occurs not only in the brain, but also in the spinal cord during the first year of interferon‐beta treatment.
    Type of Medium: Online Resource
    ISSN: 1351-5101 , 1468-1331
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2020241-6
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