Preactive lesions in multiple sclerosis

@article{VanDerValk2009PreactiveLI,
  title={Preactive lesions in multiple sclerosis},
  author={Paul Van Der Valk and Sandra Amor},
  journal={Current Opinion in Neurology},
  year={2009},
  volume={22},
  pages={207–213}
}
Purpose of reviewKnowledge of the early pathological changes observed in multiple sclerosis (MS) has advanced by implementation of many improved pathological, biochemical and imaging techniques. This review highlights the accumulating evidence for early pathological changes we term ‘preactive lesions’, characterized by clusters of activated microglia in otherwise normal-appearing white matter. Recent findingsCompelling evidence is accumulating for pathological changes in normal-appearing white… 
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References

SHOWING 1-10 OF 34 REFERENCES
Pathological abnormalities in the normal-appearing white matter in multiple sclerosis
TLDR
The hypothesis that microglial activation, as defined by altered phenotype and HLA-DR positivity, will act as a marker for oligodendrocyte/myelin and axonal pathology in MS NAWM is tested.
Molecular Changes in White Matter Adjacent to an Active Demyelinating Lesion in Early Multiple Sclerosis
TLDR
This study shows earliest molecular changes in white matter surrounding an actively demyelinating lesion during the first manifestation of MS, pointing toward a more widespread pathological process.
Immunopathology of secondary‐progressive multiple sclerosis
TLDR
Findings suggest that slowly expanding lesions (progressive plaques), in which ongoing myelin breakdown occurs in the absence of florid perivascular cell cuffing or other histological signs of acute inflammation, contribute to disease progression in cases of secondary‐progressive multiple sclerosis.
Magnetic resonance studies of abnormalities in the normal appearing white matter and grey matter in multiple sclerosis
TLDR
Quantitative structural MR techniques reveal that there are abnormalities in NAWM and NAGM, and studies correlating structural MR and fMRI parameters with measures of function in well defined anatomical pathways should further elucidate the pathogenic role of abnormality in the normal appearing tissues.
The pathogenesis of lesions and normal-appearing white matter changes in multiple sclerosis: a serial diffusion MRI study.
TLDR
The findings indicate that new focal lesions associated with frank BBB leakage are preceded by subtle, progressive alterations in tissue integrity beyond the resolution of conventional MRI.
Lesion genesis in a subset of patients with multiple sclerosis: a role for innate immunity?
TLDR
It is suggested that the areas of microglial activation represent an early stage of tissue injury, which precedes the formation of hypoxia-like demyelinated plaques in MS.
Post-mortem MRI-guided sampling of multiple sclerosis brain lesions: increased yield of active demyelinating and (p)reactive lesions.
TLDR
It is concluded that MRI-guided sampling of brain tissue increases the yield of active multiple sclerosis lesions, including active demyelinating and (p)reactive lesions.
Magnetization transfer changes in the normal appering white matter precede the appearance of enhancing lesions in patients with multiple sclerosis
TLDR
It is suggested that changes in the NAWM of patients with MS occur before lesions becomes evident on conventional MRI scans.
Staging of multiple sclerosis (MS) lesions: pathology of the time frame of MS
TLDR
It is concluded that an ideal staging system does not yet exist, and that, more than anything else, the material dictates the choice for a staging system.
...
...