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Article ; Online: Isolated cognitive impairment in people with multiple sclerosis: frequency, MRI patterns and its development over time.

Bouman, Piet M / van Dam, Maureen A / Jonkman, Laura E / Steenwijk, Martijn D / Schoonheim, Menno M / Geurts, Jeroen J G / Hulst, Hanneke E

Journal of neurology

2024 Volume 271, Issue 5, Page(s) 2159–2168

Abstract: Objectives: To study the frequency of isolated (i.e., single-domain) cognitive impairments, domain specific MRI correlates, and its longitudinal development in people with multiple sclerosis (PwMS).: Methods: 348 PwMS (mean age 48 ± 11 years, 67% ... ...

Abstract	Objectives: To study the frequency of isolated (i.e., single-domain) cognitive impairments, domain specific MRI correlates, and its longitudinal development in people with multiple sclerosis (PwMS). Methods: 348 PwMS (mean age 48 ± 11 years, 67% female, 244RR/52SP/38PP) underwent neuropsychological testing (extended BRB-N) at baseline and at five-year follow-up. At baseline, structural MRI was acquired. Isolated cognitive impairment was defined as a Z-score of at least 1.5 SD below normative data in one domain only (processing speed, memory, executive functioning/working memory, and attention). Multi-domain cognitive impairment was defined as being affected in ≥ 2 domains, and cognitively preserved otherwise. For PwMS with isolated cognitive impairment, MRI correlates were explored using linear regression. Development of isolated cognitive impairment over time was evaluated based on reliable change index. Results: At baseline, 108 (31%) PwMS displayed isolated cognitive impairment, 148 (43%) PwMS displayed multi-domain cognitive impairment. Most PwMS with isolated cognitive impairment were impaired on executive functioning/working memory (EF/WM; N = 37), followed by processing speed (IPS; N = 25), memory (N = 23), and attention (N = 23). Isolated IPS impairment was explained by a model of cortical volume and fractional anisotropy (adj. R Conclusion: Isolated cognitive impairment is frequently present in PwMS and can serve as a proxy for further decline, particularly when it concerns processing speed. Cortical and deep grey matter atrophy seem to play a pivotal role in isolated cognitive impairment. Timely detection and patient-tailored intervention, predominantly for IPS, may help to postpone further cognitive decline.
MeSH term(s)	Humans ; Female ; Middle Aged ; Male ; Cognitive Dysfunction/etiology ; Cognitive Dysfunction/diagnostic imaging ; Cognitive Dysfunction/physiopathology ; Multiple Sclerosis/diagnostic imaging ; Multiple Sclerosis/complications ; Magnetic Resonance Imaging ; Adult ; Neuropsychological Tests ; Longitudinal Studies ; Disease Progression ; Brain/diagnostic imaging ; Brain/pathology ; Follow-Up Studies ; Executive Function/physiology
Language	English
Publishing date	2024-01-30
Publishing country	Germany
Document type	Journal Article
ZDB-ID	187050-6
ISSN	1432-1459 ; 0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
ISSN (online)	1432-1459
ISSN	0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
DOI	10.1007/s00415-024-12185-8
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Article ; Online: The network collapse in multiple sclerosis: An overview of novel concepts to address disease dynamics.

Schoonheim, Menno M / Broeders, Tommy A A / Geurts, Jeroen J G

NeuroImage. Clinical

2022 Volume 35, Page(s) 103108

Abstract: Multiple sclerosis is a neuroinflammatory and neurodegenerative disorder of the central nervous system that can be considered a network disorder. In MS, lesional pathology continuously disconnects structural pathways in the brain, forming a disconnection ...

Abstract	Multiple sclerosis is a neuroinflammatory and neurodegenerative disorder of the central nervous system that can be considered a network disorder. In MS, lesional pathology continuously disconnects structural pathways in the brain, forming a disconnection syndrome. Complex functional network changes then occur that are poorly understood but closely follow clinical status. Studying these structural and functional network changes has been and remains crucial to further decipher complex symptoms like cognitive impairment and physical disability. Recent insights especially implicate the importance of monitoring network hubs in MS, like the thalamus and default-mode network which seem especially hit hard. Such network insights in MS have led to the hypothesis that as the network continues to become disconnected and dysfunctional, exceeding a certain threshold of network efficiency loss leads to a "network collapse". After this collapse, crucial network hubs become rigid and overloaded, and at the same time a faster neurodegeneration and accelerated clinical (and cognitive) progression can be seen. As network neuroscience has evolved, the MS field can now move towards a clearer classification of the network collapse itself and specific milestone events leading up to it. Such an updated network-focused conceptual framework of MS could directly impact clinical decision making as well as the design of network-tailored rehabilitation strategies. This review therefore provides an overview of recent network concepts that have enhanced our understanding of clinical progression in MS, especially focusing on cognition, as well as new concepts that will likely move the field forward in the near future.
MeSH term(s)	Brain ; Brain Mapping ; Humans ; Magnetic Resonance Imaging ; Multiple Sclerosis/pathology ; Neural Pathways
Language	English
Publishing date	2022-07-14
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2701571-3
ISSN	2213-1582 ; 2213-1582
ISSN (online)	2213-1582
ISSN	2213-1582
DOI	10.1016/j.nicl.2022.103108
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Article: Cysteine Proteases and Mitochondrial Instability: A Possible Vicious Cycle in MS Myelin?

Poerwoatmodjo, Anthony / Schenk, Geert J / Geurts, Jeroen J G / Luchicchi, Antonio

Frontiers in cellular neuroscience

2020 Volume 14, Page(s) 612383

Language	English
Publishing date	2020-12-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2020.612383
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Article ; Online: Longitudinal fibre-specific white matter damage predicts cognitive decline in multiple sclerosis.

Koubiyr, Ismail / Krijnen, Eva A / Eijlers, Anand J C / Dekker, Iris / Hulst, Hanneke E / Uitdehaag, Bernard M J / Barkhof, Frederik / Geurts, Jeroen J G / Schoonheim, Menno M

Brain communications

2024 Volume 6, Issue 1, Page(s) fcae018

Abstract: During the course of multiple sclerosis, many patients experience cognitive deficits which are not simply driven by lesion number or location. By considering the full complexity of white matter structure at macro- and microstructural levels, our ... ...

Abstract	During the course of multiple sclerosis, many patients experience cognitive deficits which are not simply driven by lesion number or location. By considering the full complexity of white matter structure at macro- and microstructural levels, our understanding of cognitive impairment in multiple sclerosis may increase substantially. Accordingly, this study aimed to investigate specific patterns of white matter degeneration, the evolution over time, the manifestation across different stages of the disease and their role in cognitive impairment using a novel fixel-based approach. Neuropsychological test scores and MRI scans including 30-direction diffusion-weighted images were collected from 327 multiple sclerosis patients (mean age = 48.34 years, 221 female) and 95 healthy controls (mean age = 45.70 years, 55 female). Of those, 233 patients and 61 healthy controls had similar follow-up assessments 5 years after. Patients scoring 1.5 or 2 standard deviations below healthy controls on at least two out of seven cognitive domains (from the Brief Repeatable Battery of Neuropsychological Tests, BRB-N) were classified as mildly cognitively impaired or cognitively impaired, respectively, or otherwise cognitively preserved. Fixel-based analysis of diffusion data was used to calculate fibre-specific measures (fibre density, reflecting microstructural diffuse axonal damage; fibre cross-section, reflecting macrostructural tract atrophy) within atlas-based white matter tracts at each visit. At baseline, all fixel-based measures were significantly worse in multiple sclerosis compared with healthy controls (
Language	English
Publishing date	2024-01-27
Publishing country	England
Document type	Journal Article
ISSN	2632-1297
ISSN (online)	2632-1297
DOI	10.1093/braincomms/fcae018
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Article ; Online: Artificial double inversion recovery images can substitute conventionally acquired images: an MRI-histology study.

Bouman, Piet M / Steenwijk, Martijn D / Geurts, Jeroen J G / Jonkman, Laura E

Scientific reports

2022 Volume 12, Issue 1, Page(s) 2620

Abstract: Cortical multiple sclerosis lesions are disease-specific, yet inconspicuous on magnetic resonance images (MRI). Double inversion recovery (DIR) images are sensitive, but often unavailable in clinical routine and clinical trials. Artificially generated ... ...

Abstract	Cortical multiple sclerosis lesions are disease-specific, yet inconspicuous on magnetic resonance images (MRI). Double inversion recovery (DIR) images are sensitive, but often unavailable in clinical routine and clinical trials. Artificially generated images can mitigate this issue, but lack histopathological validation. In this work, artificial DIR images were generated from postmortem 3D-T1 and proton-density (PD)/T2 or 3D-T1 and 3D fluid-inversion recovery (FLAIR) images, using a generative adversarial network. All sequences were scored for cortical lesions, blinded to histopathology. Subsequently, tissue samples were stained for proteolipid protein (myelin) and scored for cortical lesions type I-IV (leukocortical, intracortical, subpial and cortex-spanning, respectively). Histopathological scorings were then (unblinded) compared to MRI using linear mixed models. Images from 38 patients (26 female, mean age 64.3 ± 10.7) were included. A total of 142 cortical lesions were detected, predominantly subpial. Histopathology-blinded/unblinded sensitivity was 13.4/35.2% for artificial DIR generated from T1-PD/T2, 14.1/41.5% for artificial DIR from T1-FLAIR, 17.6/49.3% for conventional DIR and 10.6/34.5% for 3D-T1. When blinded to histopathology, there were no differences; with histopathological feedback at hand, conventional DIR and artificial DIR from T1-FLAIR outperformed the other sequences. Differences between histopathology-blinded/unblinded sensitivity could be minified through adjustment of the scoring criteria. In conclusion, artificial DIR images, particularly generated from T1-FLAIR could potentially substitute conventional DIR images when these are unavailable.
MeSH term(s)	Aged ; Cerebral Cortex/diagnostic imaging ; Cerebral Cortex/pathology ; Diagnosis ; Diffusion Tensor Imaging/methods ; Female ; Histological Techniques/methods ; Humans ; Image Processing, Computer-Assisted/methods ; Imaging, Three-Dimensional/methods ; Male ; Middle Aged ; Multiple Sclerosis/diagnostic imaging ; Multiple Sclerosis/pathology ; Neuroimaging/methods ; Sensitivity and Specificity
Language	English
Publishing date	2022-02-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-06546-4
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Article ; Online: Task- and resting-state fMRI studies in multiple sclerosis: From regions to systems and time-varying analysis. Current status and future perspective.

Rocca, Maria A / Schoonheim, Menno M / Valsasina, Paola / Geurts, Jeroen J G / Filippi, Massimo

NeuroImage. Clinical

2022 Volume 35, Page(s) 103076

Abstract: Multiple sclerosis (MS) is a neurological disorder affecting the central nervous system and features extensive functional brain changes that are poorly understood but relate strongly to clinical impairments. Functional magnetic resonance imaging (fMRI) ... ...

Abstract	Multiple sclerosis (MS) is a neurological disorder affecting the central nervous system and features extensive functional brain changes that are poorly understood but relate strongly to clinical impairments. Functional magnetic resonance imaging (fMRI) is a non-invasive, powerful technique able to map activity of brain regions and to assess how such regions interact for an efficient brain network. FMRI has been widely applied to study functional brain changes in MS, allowing to investigate functional plasticity consequent to disease-related structural injury. The first studies in MS using active fMRI tasks mainly aimed to study such plastic changes by identifying abnormal activity in salient brain regions (or systems) involved by the task. In later studies the focus shifted towards resting state (RS) functional connectivity (FC) studies, which aimed to map large-scale functional networks of the brain and to establish how MS pathology impairs functional integration, eventually leading to the hypothesized network collapse as patients clinically progress. This review provides a summary of the main findings from studies using task-based and RS fMRI and illustrates how functional brain alterations relate to clinical disability and cognitive deficits in this condition. We also give an overview of longitudinal studies that used task-based and RS fMRI to monitor disease evolution and effects of motor and cognitive rehabilitation. In addition, we discuss the results of studies using newer technologies involving time-varying FC to investigate abnormal dynamism and flexibility of network configurations in MS. Finally, we show some preliminary results from two recent topics (i.e., multimodal MRI analysis and artificial intelligence) that are receiving increasing attention. Together, these functional studies could provide new (conceptual) insights into disease stage-specific mechanisms underlying progression in MS, with recommendations for future research.
MeSH term(s)	Artificial Intelligence ; Brain ; Brain Mapping ; Humans ; Magnetic Resonance Imaging/methods ; Multiple Sclerosis/pathology
Language	English
Publishing date	2022-06-06
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2701571-3
ISSN	2213-1582 ; 2213-1582
ISSN (online)	2213-1582
ISSN	2213-1582
DOI	10.1016/j.nicl.2022.103076
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Article ; Online: Comparison of videolaryngoscopy alone with video-assisted fibreoptic intubation in a difficult cadaver airway model.

Koopman, Erik M / van Emden, Michael W / Geurts, Jeroen J G / Schwarte, Lothar A / Schober, Patrick

European journal of anaesthesiology

2021 Volume 38, Issue 3, Page(s) 318–319

Abstract: Abstract: No Abstract. ...

Abstract	Abstract: No Abstract.
MeSH term(s)	Cadaver ; Fiber Optic Technology ; Humans ; Intubation, Intratracheal ; Laryngoscopes ; Laryngoscopy
Language	English
Publishing date	2021-02-01
Publishing country	England
Document type	Journal Article
ZDB-ID	605770-6
ISSN	1365-2346 ; 0265-0215
ISSN (online)	1365-2346
ISSN	0265-0215
DOI	10.1097/EJA.0000000000001333
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Article ; Online: Artificial double inversion recovery images can substitute conventionally acquired images

Piet M. Bouman / Martijn D. Steenwijk / Jeroen J. G. Geurts / Laura E. Jonkman

Scientific Reports, Vol 12, Iss 1, Pp 1-

an MRI-histology study

2022 Volume 9

Abstract: Abstract Cortical multiple sclerosis lesions are disease-specific, yet inconspicuous on magnetic resonance images (MRI). Double inversion recovery (DIR) images are sensitive, but often unavailable in clinical routine and clinical trials. Artificially ... ...

Abstract	Abstract Cortical multiple sclerosis lesions are disease-specific, yet inconspicuous on magnetic resonance images (MRI). Double inversion recovery (DIR) images are sensitive, but often unavailable in clinical routine and clinical trials. Artificially generated images can mitigate this issue, but lack histopathological validation. In this work, artificial DIR images were generated from postmortem 3D-T1 and proton-density (PD)/T2 or 3D-T1 and 3D fluid-inversion recovery (FLAIR) images, using a generative adversarial network. All sequences were scored for cortical lesions, blinded to histopathology. Subsequently, tissue samples were stained for proteolipid protein (myelin) and scored for cortical lesions type I-IV (leukocortical, intracortical, subpial and cortex-spanning, respectively). Histopathological scorings were then (unblinded) compared to MRI using linear mixed models. Images from 38 patients (26 female, mean age 64.3 ± 10.7) were included. A total of 142 cortical lesions were detected, predominantly subpial. Histopathology-blinded/unblinded sensitivity was 13.4/35.2% for artificial DIR generated from T1-PD/T2, 14.1/41.5% for artificial DIR from T1-FLAIR, 17.6/49.3% for conventional DIR and 10.6/34.5% for 3D-T1. When blinded to histopathology, there were no differences; with histopathological feedback at hand, conventional DIR and artificial DIR from T1-FLAIR outperformed the other sequences. Differences between histopathology-blinded/unblinded sensitivity could be minified through adjustment of the scoring criteria. In conclusion, artificial DIR images, particularly generated from T1-FLAIR could potentially substitute conventional DIR images when these are unavailable.
Keywords	Medicine ; R ; Science ; Q
Subject code	571 ; 610
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The network collapse in multiple sclerosis

Menno M. Schoonheim / Tommy A.A. Broeders / Jeroen J.G. Geurts

NeuroImage: Clinical, Vol 35, Iss , Pp 103108- (2022)

An overview of novel concepts to address disease dynamics

2022

Abstract	Multiple sclerosis is a neuroinflammatory and neurodegenerative disorder of the central nervous system that can be considered a network disorder. In MS, lesional pathology continuously disconnects structural pathways in the brain, forming a disconnection syndrome. Complex functional network changes then occur that are poorly understood but closely follow clinical status. Studying these structural and functional network changes has been and remains crucial to further decipher complex symptoms like cognitive impairment and physical disability. Recent insights especially implicate the importance of monitoring network hubs in MS, like the thalamus and default-mode network which seem especially hit hard. Such network insights in MS have led to the hypothesis that as the network continues to become disconnected and dysfunctional, exceeding a certain threshold of network efficiency loss leads to a “network collapse”. After this collapse, crucial network hubs become rigid and overloaded, and at the same time a faster neurodegeneration and accelerated clinical (and cognitive) progression can be seen. As network neuroscience has evolved, the MS field can now move towards a clearer classification of the network collapse itself and specific milestone events leading up to it. Such an updated network-focused conceptual framework of MS could directly impact clinical decision making as well as the design of network-tailored rehabilitation strategies. This review therefore provides an overview of recent network concepts that have enhanced our understanding of clinical progression in MS, especially focusing on cognition, as well as new concepts that will likely move the field forward in the near future.
Keywords	Multiple sclerosis ; Network ; Connectivity ; Hub ; Efficiency ; Cognition ; Computer applications to medicine. Medical informatics ; R858-859.7 ; Neurology. Diseases of the nervous system ; RC346-429
Subject code	000
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Task- and resting-state fMRI studies in multiple sclerosis

Maria A. Rocca / Menno M. Schoonheim / Paola Valsasina / Jeroen J.G. Geurts / Massimo Filippi

NeuroImage: Clinical, Vol 35, Iss , Pp 103076- (2022)

From regions to systems and time-varying analysis. Current status and future perspective

2022

Abstract	Multiple sclerosis (MS) is a neurological disorder affecting the central nervous system and features extensive functional brain changes that are poorly understood but relate strongly to clinical impairments. Functional magnetic resonance imaging (fMRI) is a non-invasive, powerful technique able to map activity of brain regions and to assess how such regions interact for an efficient brain network. FMRI has been widely applied to study functional brain changes in MS, allowing to investigate functional plasticity consequent to disease-related structural injury. The first studies in MS using active fMRI tasks mainly aimed to study such plastic changes by identifying abnormal activity in salient brain regions (or systems) involved by the task. In later studies the focus shifted towards resting state (RS) functional connectivity (FC) studies, which aimed to map large-scale functional networks of the brain and to establish how MS pathology impairs functional integration, eventually leading to the hypothesized network collapse as patients clinically progress. This review provides a summary of the main findings from studies using task-based and RS fMRI and illustrates how functional brain alterations relate to clinical disability and cognitive deficits in this condition. We also give an overview of longitudinal studies that used task-based and RS fMRI to monitor disease evolution and effects of motor and cognitive rehabilitation. In addition, we discuss the results of studies using newer technologies involving time-varying FC to investigate abnormal dynamism and flexibility of network configurations in MS. Finally, we show some preliminary results from two recent topics (i.e., multimodal MRI analysis and artificial intelligence) that are receiving increasing attention. Together, these functional studies could provide new (conceptual) insights into disease stage-specific mechanisms underlying progression in MS, with recommendations for future research.
Keywords	Multiple sclerosis ; Functional MRI ; Resting-state fMRI ; Task fMRI ; Computer applications to medicine. Medical informatics ; R858-859.7 ; Neurology. Diseases of the nervous system ; RC346-429
Subject code	610
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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