Rows show duration in weeks of acute A and subacute phases B , as defined in Fig. Analogous concentric patterns and a faster recovery at the periphery of the lesion are apparent. Note that the duration of the acute phase is far shorter 4 weeks or less than that of the subacute phase up to 20 weeks. Patterns of lesion formation, comparing peak and residual hyperintensity, for the same 3 lesions as shown in Fig.
Multiple sclerosis: tissue destruction and repair. Reviewed by K. Dedman. Copyright and License information ▻ Disclaimer · Copyright notice. Multiple sclerosis: tissue destruction and repair is the proceedings of the joint meeting of ECTRIMS and ACTRIMS (European and American Committees for.
Peak a and residual hyperintensities b are shown in rows. Concentric patterns and a correlation between higher levels of intensity and greater residual are apparent ie, residual damage [ b ] tends to occur in areas of maximal hyperintensity. Also, note how the proportions of residual damage are disproportionally smaller for larger lesions. To illustrate the effect of the size of the lesion, 3 example lesions of different peak sizes are also shown. Note how residual hyperintensity is disproportionately smaller for larger lesions and concentrated in the center of the lesion. Recovery ie, return toward isointensity at the periphery of the lesion not only occurs more comprehensively, but also faster Fig.
This pattern is akin to concentric patterns described on histopathologic studies, such as active edges of plaque with accumulating macrophages 21 and rims of remyelination. The residual hyperintensity left by small lesions was disproportionately greater than that of larger lesions Fig.
This finding would suggest that many small new lesions constitute more destructive activity than equivalent new lesion burden in the form of few large lesions. Bearing in mind that T2 hyperintensity alone cannot be attributed to tissue damage directly, we sought to test this hypothesis further via a link to clinical disability EDSS and phenotype relapsing or progressive. If these 2 classes differ in their destructive potential, we would expect to see differences in the amount of residual hyperintensity and, possibly, in the level of disability.
This feature was indeed observed: The significantly higher disability of the progressive cohort on-line Table 1 introduces inevitable bias to the comparison shown in Fig. When considering this bias in a 2-factor analysis of variance as well as by excluding the 5 subjects with progressive disease green color in Fig. Boxes and P values in green show analysis with the progressive group excluded as a result of the unbalanced design with regard to Expanded Disability Status Scale [EDSS]; see on-line Table 1. Relationships to clinical subtypes were tested via the mean values of all dynamic features, averaged over all lesions in a patient.
Overall, lesions in progressive MS seem to behave differently; they occur less frequently but tend to be smaller and more persistent. Lesions in SPMS seem to undergo shorter and less intense dynamic changes of waxing and waning, consistent with a reduced inflammatory response. They did not differ significantly from SPMS in any of the tested lesion dynamics, though residual and peak hyperintensity showed a borderline trend to be higher in PPMS on-line Table 3. Do these new short-term T2 properties relate to long-term progression of disease?
We examined relationships of new lesion dynamics with disability and atrophy and rates thereof. Greater amounts of lesion recovery less residual hyperintensity were associated with lower rates of atrophy and lower overall disability Fig. Relationships with progression of disability did not reach significance. Short-term lesion recovery related to progression of atrophy and disability. B, Lesions with higher residual hyperintensity lower recovery were associated with faster rates of atrophy progression as well as greater disability.
Boxes and P values in green show t test analysis with progressive patients excluded. The duration of contrast enhancement was not equivalent to T2 activity, which continued long after active inflammation breakdown of blood-brain barrier had subsided Fig. This previously uncharacterized subacute phase suggests valuable information in the T2-signal intensity dynamic beyond the pure inflammatory component, as measured by contrast enhancement. The acute phase lasted less than 2 weeks on average, whereas the subacute phase lasted substantially longer, ranging from 3 to 10 weeks on average.
The week duration of overall T2 activity, defined here as the sum of acute and subacute periods, is in agreement with the 8- to week waning phases observed qualitatively in previous studies. Fate and temporal extent of individual lesion portions can be very different, as illustrated by the feature maps in Fig. In a similar fashion, the use of global lesion burden as a surrogate for severity of disease seems problematic, particularly in the light of the observed disassociation between the peak size and the residual of a lesion. Our findings suggest that the number and volume of a lesion capture partially different aspects of disease activity, and thus MR imaging surrogates of the severity and activity of disease would benefit from reporting both, to capture the different impact of small versus large lesions.
The presented measurements of duration also have direct implications on study design and possibly evaluation of therapy: Consequently, studies seeking to use longitudinal comparison of lesion recovery should have follow-up intervals of 3 months or less. The present findings of heterogeneous Fig.
To the extent that peak lesion size relates to the intensity of the inflammatory response, larger lesions become indicative of stronger immune activity but also greater repair ie, a case with many small new lesions could represent worse [more destructive] disease activity than a case with a few large new lesions of equivalent total size. Recently, positive aspects of inflammation have been proffered in the pathogenesis of MS. This could also partly explain the disassociation between relapses and the presence of enhancing lesions, 5 in which relapses are commonly accompanied with enhancing lesions but not vice versa.
Evidence is also surfacing that response to therapy varies with immunopathologic subtype of a lesion, 26 which further invites the search for in vivo surrogates capable of dissociating the presence of inflammation from its true effect on irreversible destruction of tissue. Recent histopathologic studies found repair to be extensive irrespective of duration of disease. However, because the new myelin was found on histologic studies to be thinner and more sparsely structured, and predominant around the rim of the lesion, a contribution of remyelination toward change in T2 intensity remains feasible ie, the observed residual may stem from only partial remyelination.
However, the extended range of the subacute phase spectrum after 3 months is also compatible with T2 changes reflecting processes other than water resorption eg, remyelination and gliosis. The observed trend of lowest to highest residual in RR, SP, and PPMS, respectively, would indirectly support models that consider PPMS as etiologically distinct, rather than as a form of SPMS in which the relapsing phase remained subclinical, though a larger cohort with balanced duration of disease would be necessary to test this effect more reliably.
Taken together, these findings are consistent with models that attribute inflammation and degeneration as the dominant processes in relapsing and progressive MS, respectively, and clinical progression as an exhaustion of reparatory potential. Therefore, a therapeutic effect may be more readily apparent as a change in lesion dynamics, recovery rate, and level, rather than as a change in total lesion burden or number of enhancing lesions.
Our study examined the short-term behavior of T2 lesions, obtained by time series modeling of voxel-based intensity change, in the context of degenerative and reparatory processes, and tested for relationships to long-term progression of disease.
The following findings emerged:. Concentric spatial patterns of hyperintensity, residual, and evolution dynamics were observed, similar to patterns observed on histopathologic examination.
New lesions that leave less residual hyperintensity were associated with both lower progression rates of atrophy BPF change per year and lower levels of disability EDSS. Ferenc Jolesz for providing the longitudinal MR imaging data, and Sandra Cook for assistance with reviewing clinical records. We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail.
We do not capture any email address. This article has not yet been cited by articles in journals that are participating in Crossref Cited-by Linking. Skip to main content. Materials and Methods Patients, Image Acquisition, and Preprocessing We obtained MR imaging datasets from 40 patients for 3 to 4 years, with frequent weekly to monthly examinations during the first year.
Identification of Lesions and Model Fitting We included only lesions that newly appeared during the first 6 months of the study. Results We observed a total of new lesions in 30 patients; 10 patients had no new lesions during the 1-year follow-up, excluding 38 new lesions that appeared later than 6 months past baseline. T2 Activity Continues Long after Contrast Enhancement We first sought to determine how short-term evolution of T2 lesions differs from that of contrast enhancement. The Evolution of the Lesion Shows Concentric Patterns Similar to Histopathologic Studies We found substantial heterogeneity in the spatial distribution of dynamics within a newly forming lesion.
Dynamics of T2 Lesions Differ between Clinical Phenotypes of MS Relationships to clinical subtypes were tested via the mean values of all dynamic features, averaged over all lesions in a patient.
Links to Long-Term Atrophy and Disability Do these new short-term T2 properties relate to long-term progression of disease? Discussion The duration of contrast enhancement was not equivalent to T2 activity, which continued long after active inflammation breakdown of blood-brain barrier had subsided Fig. Is Inflammation Indicative of Destruction or Repair? Conclusion Our study examined the short-term behavior of T2 lesions, obtained by time series modeling of voxel-based intensity change, in the context of degenerative and reparatory processes, and tested for relationships to long-term progression of disease.
The following findings emerged: The duration of new T2 activity exceeded that of contrast enhancement at least 2-fold. Acknowledgments We thank Dr. Indicates article with supplemental on-line tables. Axonal transection in the lesions of multiple sclerosis. N Engl J Med ; A longitudinal study of abnormalities on MRI and disability from multiple sclerosis. Characterizing the mechanisms of progression in multiple sclerosis: Arch Neurol ; Significance of T2 lesions in multiple sclerosis: A year longitudinal study.
Ann Neurol ; Relapses and progression of disability in multiple sclerosis. The natural history of multiple sclerosis: Clinical course and disability.
Brain ; Enhancing patterns in multiple sclerosis: Patterns of lesion development in multiple sclerosis: Evolution of T1 black holes in patients with multiple sclerosis imaged monthly for 4 years. Serial magnetic resonance imaging in multiple sclerosis: J Neuroimmunol ; The effect of interferon beta-1b treatment on MRI measures of cerebral atrophy in secondary progressive multiple sclerosis. European Study Group on Interferon beta-1b in secondary progressive multiple sclerosis.
Whole brain volume changes in patients with progressive MS treated with cladribine. Neurology ; Immunopathology of secondary-progressive multiple sclerosis. Remyelination is extensive in a subset of multiple sclerosis patients [published erratum appears in Brain ; Recent neuropathological findings in MS—implications for diagnosis and therapy. J Neurol ; Suppl 4: MRI time series modeling of MS lesion development.
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