Pathophysiology of inflammation and tissue injury in multiple sclerosis: What are the targets for therapy

Lassmann, Hans

doi:10.1016/j.jns.2010.07.023

Cited by 42 publications

(29 citation statements)

References 37 publications

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“…The disease progresses to the relapsing-remitting phase, which is characterized by attacks separated by periods of no clinical symptoms. This phase can last for decades, and it is characterized by inflammatory demyelination that results in the formation of demyelinating plaques in the white matter (Lassmann, 2011; Lassmann and Bradl, 2016; Libbey et al, 2014). Increased demyelination and axonal loss are found when disease involves a progressive clinical course (primary progressive or secondary progressive) and just a few options for treatment are available at this stage of the disease.…”

Section: Multiple Sclerosismentioning

confidence: 99%

Theiler's murine encephalomyelitis virus infection of SJL/J and C57BL/6J mice: Models for multiple sclerosis and epilepsy

DePaula-Silva

Hanak

Libbey

et al. 2017

Journal of Neuroimmunology

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Mouse models are great tools to study the mechanisms of disease development. Theiler’s murine encephalomyelitis virus is used in two distinct viral infection mouse models to study the human diseases multiple sclerosis (MS) and epilepsy. Intracerebral (i.c.) infection of the SJL/J mouse strain results in persistent viral infection of the central nervous system and a MS-like disease, while i.c. infection of the C57BL/6J mouse strain results in acute seizures and epilepsy. Our understanding of how the immune system contributes to the development of two disparate diseases caused by the same virus is presented.

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Section: Multiple Sclerosismentioning

confidence: 99%

Theiler's murine encephalomyelitis virus infection of SJL/J and C57BL/6J mice: Models for multiple sclerosis and epilepsy

DePaula-Silva

Hanak

Libbey

et al. 2017

Journal of Neuroimmunology

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“…[64][65][66] For example, the degree of increase in fMRI activity has been reported to be proportional to the sensitivity of T2 lesion load up to a critical limit, at which time these important compensatory mechanisms (ie, plasticity) fail. 34 Gray matter lesion conspicuity is increased with DIR techniques as well as with ultraMoreover, it is likely that an inflammatory component of disease is present either always or at some time in all stages of MS. [20][21][22][23][24] Indeed, Gd+ lesions, which indicate both an abnormality in blood-brain barrier (BBB) and central nervous system (CNS) inflammation, can occur not only in RRMS but in all Lublin-Reingold forms of MS, including in 14.1% to 42% of patients with PPMS. [12][13][14] Pathologically inflammatory CNS lesions have also been described in all forms of MS, with or without the presence of Gd+ lesions, although the distribution of inflammatory lesions can vary in location or intensity in different forms of the disease.…”

Section: Background Historical Evolution Of Ms Diagnostic Criteriamentioning

confidence: 99%

“…[12][13][14] Pathologically inflammatory CNS lesions have also been described in all forms of MS, with or without the presence of Gd+ lesions, although the distribution of inflammatory lesions can vary in location or intensity in different forms of the disease. [20][21][22][23][24] When sensitive and frequent MRI studies are performed, Gd+ and unequivocally new or enlarging T2 brain lesions (subclinical relapses) can occur much more commonly than clinical symptoms (relapses or progression). [25][26][27][28] This may be explained at least in part by several factors: lesions in "eloquent" brain areas such as the optic nerves are more likely to be clinically expressed than lesions in less eloquent pathways; the degree of matrix and axonal destruction may vary; and the potential exists for rapid symptom recovery.…”

Section: Background Historical Evolution Of Ms Diagnostic Criteriamentioning

confidence: 99%

Use of Magnetic Resonance Imaging as Well as Clinical Disease Activity in the Clinical Classification of Multiple Sclerosis and Assessment of Its Course

Cook¹,

Dhib‐Jalbut²,

Dowling³

et al. 2012

International Journal of MS Care

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It has recently been suggested that the Lublin-Reingold clinical classification of multiple sclerosis (MS) be modified to include the use of magnetic resonance imaging (MRI). An international consensus conference sponsored by the Consortium of Multiple Sclerosis Centers (CMSC) was held from March 5to 7, 2010, to review the available evidence on the need for such modification of the Lublin-Reingold criteria and whether the addition of MRI or other biomarkers might lead to a better understanding of MS pathophysiology and disease course over time. The conference participants concluded that evidence of new MRI gadolinium-enhancing (Gd+) T1-weighted lesions and unequivocally new or enlarging T2-weighted lesions (subclinical activity, subclinical relapses) should be added to the clinical classification of MS in distinguishing relapsing inflammatory from progressive forms of the disease. The consensus was that these changes to the classification system would provide more rigorous definitions and categorization of MS course, leading to better insights as to the evolution and treatment of MS. Int J MS Care. 2012;14:105-114. It was recently suggested by Lincoln et al. 1 that the Lublin-Reingold clinical classification of multiple sclerosis (MS) 2 for the assessment of MS phenotypes and patient evolution over time be modified to include magnetic resonance imaging (MRI). It was recommended that the classification incorporate the "conventional," generally available MRI techniques of gadolinium (Gd) T1-weighted sequences and dual-echo and fluid-attenuated inversion recovery (T2-weighted and FLAIR) images ( course over time and, in turn, more informed clinical trials and a better understanding of appropriate therapies.Prior to the meeting, a survey of members of the CMSC was conducted on the need to modify the Lublin-Reingold classification. Over a 1-week period, 141 responses were received, representing 16% of the CMSC members polled. The results were as follows: A total of 70% of respondents indicated that the LublinReingold classification did not sufficiently distinguish the different forms of MS; 87% felt that the LublinReingold classification did not sufficiently distinguish MS disease activity even within a given category of the disease; and 84% indicated that it would be useful to include certain subclinical indices of disease activity in the clinical classification, such as MRI gadoliniumother MRI modalities that are not currently widely available and other validated biomarkers might be added to the classification in the future.In response to the publication of Lincoln et al., 1 the Consortium of Multiple Sclerosis Centers (CMSC) sponsored an international consensus conference, which was held in Short Hills, New Jersey, from March 5 to 7, 2010. Participating in the conference were 28 invited MS experts from North and South America and Europe who were well versed in clinical trials, the management of MS, biostatistics, neuropathology, neuroimaging, and neuroimmunology. The goal of the meeting was to review the available...

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“…It has been shown that axonal injury, myelin destruction and vascular involvement occur in multiple sclerosis (MS) to a variable extent in MR-visible lesions and beyond them (Lassmann, 2011a, 2011b, 2011c). Brain atrophy (Bermel and Bakshi, 2006; Fisher et al, 2008; Miller et al, 2002) and a global reduction of cerebral blood flow (CBF) (Coisne and Engelhardt, 2011; D’Haeseleer et al, 2011; Nico and Ribatti, 2012) were reported in both gray (GM) and white matter (WM) areas in patients with MS. Damage to the blood–brain barrier (BBB) in patients with MS in areas corresponding to MR-visible lesions is frequently seen as contrast-enhanced area on longitudinal relaxation time (T1)-weighted MRI (Brochet et al, 2008; Filippi and Grossman, 2002; Filippi et al, 2011; Nessler et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Quantification of blood-to-brain transfer rate in multiple sclerosis

Taheri

Rosenberg

Ford

2013

Multiple Sclerosis and Related Disorders

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Blood–brain barrier (BBB) disruption visualized in lesions by MRI is a major biomarker of disease activity in multiple sclerosis (MS). However, in MS, destruction occurs to a variable extent in lesions as well as in gray matter (GM) and in the normal appearing white matter (NAWM). A method to quantify the BBB disruption in lesions as well as in non-lesion areas would be useful for assessment of MS progression and treatments. The objective of this study was to quantify the BBB transfer rate (Ki) in WM lesions, in the NAWM, and in the full-brain of MS patients. Thirteen MS patients with active lesions and 10 healthy controls with age and gender matching were recruited for full-brain and WM Ki studies. Dynamic contrast-enhanced MRI (DCEMRI) scans were conducted using T1 mapping with partial inversion recovery (TAPIR), a fast T1 mapping technique, following administration of a quarter-dose of the contrast agent Gadolinium-DTPA (Gd-DTPA). The Patlak modeling technique was used to derive a voxel-based map of Ki. In all patients contrast-enhanced lesions, quantified by Ki maps, were observed. Compared with controls, patients with MS exhibited an increase in mean Ki of the full-brain (P-value<0.05) but no significant difference in mean Ki of NAWM. The identified increase in full-brain Ki of MS patients suggests a global vascular involvement associated with MS disease. The lack of observed significant decrease in Ki in NAWM suggests lower involvement of WM vasculature than full-brain vasculature in MS. Ki maps constructed from time series data acquired by DCEMRI provide additional information about BBB that could be used for evaluation of vascular involvement in MS and monitoring treatment effectiveness.

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Pathophysiology of inflammation and tissue injury in multiple sclerosis: What are the targets for therapy

Cited by 42 publications

References 37 publications

Theiler's murine encephalomyelitis virus infection of SJL/J and C57BL/6J mice: Models for multiple sclerosis and epilepsy

Theiler's murine encephalomyelitis virus infection of SJL/J and C57BL/6J mice: Models for multiple sclerosis and epilepsy

Use of Magnetic Resonance Imaging as Well as Clinical Disease Activity in the Clinical Classification of Multiple Sclerosis and Assessment of Its Course

Quantification of blood-to-brain transfer rate in multiple sclerosis

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