White matter and lesion T1 relaxation times increase in parallel and correlate with disability in multiple sclerosis

Parry, Allyson; Clare, Stuart; Jenkinson, Mark; Smith, Stephen M.; Palace, Jacqueline; Matthews, Paul M.

doi:10.1007/s00415-002-0837-7

Cited by 97 publications

(100 citation statements)

References 37 publications

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“…Astrocytosis, which occurs with age and following acute ischemia, has been coupled with increased T1 relaxation times Sibson et al, 2008) although increased T1 values are also associated with axonal loss, at least in white matter (van Walderveen et al, 1998), edema (Barnes and McDonald, 1988), and the lesions which characterize multiple sclerosis (Parry et al, 2002). The evidence presented here indicates that the relationship between T1 and age is not straightforward, with evidence of little change in older age and an increase in middle age.…”

Section: Discussionmentioning

confidence: 68%

The age-related deficit in LTP is associated with changes in perfusion and blood-brain barrier permeability

Blau¹,

Cowley²,

O'Sullivan³

et al. 2012

Neurobiology of Aging

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In view of the increase in the aging population and the unavoidable parallel increase in the incidence of age-related neurodegenerative diseases, a key challenge in neuroscience is the identification of clinical signatures which change with age and impact on neuronal and cognitive function. Early diagnosis offers the possibility of early therapeutic intervention, thus magnetic resonance imaging (MRI) is potentially a powerful diagnostic tool. We evaluated age-related changes in relaxometry, blood flow, and blood-brain barrier (BBB) permeability in the rat by magnetic resonance imaging and assessed these changes in the context of the age-related decrease in synaptic plasticity. We report that T2 relaxation time was decreased with age; this was coupled with a decrease in gray matter perfusion, suggesting that the observed microglial activation, as identified by increased expression of CD11b, MHCII, and CD68 by immunohistochemistry, flow cytometry, or polymerase chain reaction (PCR), might be a downstream consequence of these changes. Increased permeability of the blood-brain barrier was observed in the perivascular area and the hippocampus of aged, compared with young, rats. Similarly there was an age-related increase in CD45-positive cells by flow cytometry, which are most likely infiltrating macrophages, with a parallel increase in the messenger mRNA expression of chemokines IP-10 and MCP-1. These combined changes may contribute to the deficit in long-term potentiation (LTP) in perforant path-granule cell synapses of aged animals.

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Section: Discussionmentioning

confidence: 68%

The age-related deficit in LTP is associated with changes in perfusion and blood-brain barrier permeability

Blau¹,

Cowley²,

O'Sullivan³

et al. 2012

Neurobiology of Aging

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“…These changes after axonal loss can involve local synaptic reorganization, reorganization at more distant sites, or recruitment of parallel existing pathways (33), hampering relations between the location of an original lesion and its remaining symptoms after the development of adaptation. Importantly, diffuse pathology in the NAWM, which may also contribute to disability (35,36) is not included in total lesional disease burden (12).…”

Section: Discussionmentioning

confidence: 99%

Clinical correlations of brain lesion distribution in multiple sclerosis

Vellinga¹,

Geurts²,

Rostrup

et al. 2009

Magnetic Resonance Imaging

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Purpose: To explore relations between spatial distribution of multiple sclerosis (MS) lesions, and disability. In MS, the presence of asymptomatic brain lesions challenges the prediction of disability based on conventional brain MRI. Hypothesizing that symptomatology may partly be determined by lesion location, this retrospective study explored relations between lesion location and disability using voxelwise analyses in standard space. Materials and Methods:Using nonparametric permutation-based statistics, voxelwise lesion probability on T2 lesion masks was related to expanded disability status scale (EDSS) and MS functional composite (MSFC) subdomain scores and demographic characteristics of 325 MS patients. To identify statistically significant locations, a cluster-forming threshold of 3.1 was used. Results:In clusters in the periventricular region, lesion probability correlated significantly (P Ͻ 0.001) with disability and disease duration, and was higher in progressive than in relapsing disease. When controlled for lesion load (LL), no significant clusters survived. Presence and number of spinal cord lesions did not correlate with lesion probability in any location, and did not influence correlations with disability when included in its analyses.Conclusion: Periventricular lesions were related to disability. LL influenced relations between disability and lesion probability throughout the brain, suggesting interplay between lesional burden and its location in determining disability in MS.

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“…71 Even in normal-appearing white matter, abnormalities have been detected with DTI, MTI, and pathologic analysis that may be associated with clinical and cognitive worsening. [72][73][74] In summary, a limited number of studies of classic MRI abnormalities show CNS pathology, with virtually all MRI lesions being associated with CNS injury of varying degrees. It is hoped that other easily obtained biomarkers will also emerge over time, 75 particularly as the etiology and pathophysiology of the disease become better understood.…”

Section: Evidence That the Ms Mri-clinical Paradox Is Disappearing Inmentioning

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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White matter and lesion T1 relaxation times increase in parallel and correlate with disability in multiple sclerosis

Cited by 97 publications

References 37 publications

The age-related deficit in LTP is associated with changes in perfusion and blood-brain barrier permeability

The age-related deficit in LTP is associated with changes in perfusion and blood-brain barrier permeability

Clinical correlations of brain lesion distribution in multiple sclerosis

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

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