Post-mortem MRI-guided sampling of multiple sclerosis brain lesions - Increased yield of active demyelinating and (p)reactive lesions

Macroscopic sampling of multiple sclerosis lesions in the brain tends to fi nd chronic lesions. For a better understanding of the dynamics of the multi ple sclerosis disease process, research into new and developing lesions is of great interest. As MRI in vivo effectively demonstrates lesions in multi ple sclerosis patients, we have applied it to unfixed post-mortem brain sli ces to identify abnormalities, in order to obtain a higher yield of. active lesions. The Netherlands Brain Bank organized the rapid autopsy of 29 mult iple sclerosis patients. The brain was cut in 1 cm coronal slices. One or t wo slices were subjected to T-1- and T-2-weighted MRI, and then cut at the plane of the MRI scan into 5 mm thick opposing sections. Areas of interest were identified based on the MRI findings and excised. One half was fixed i n 10% formalin and paraffin-embedded, and the corresponding area in the adj acent half was snap-frozen in liquid nitrogen. In total, 136 out of 174 bra in tissue samples could be matched with the abnormalities seen on T-2-weigh ted MRIs. The stage of lesional development was determined (immuno) histoch emically. For 54 MRI-detectable samples, it was recorded whether they were macroscopically detectable, i.e. visible and/or palpable. Histopathological analysis revealed that 48% of the hyperintense areas seen on T2-weighted i mages represented active lesions, including lesions localized in the normal appearing white matter, without apparent loss of myelin but nevertheless s howing a variable degree of oedema, small clusters of microglial cells with enhanced major histocompatibility complex class II antigen, CD45 and CD68 antigen expression and a variable number of perivascular lymphocytes around small blood vessels [designated as (p)reactive lesions]. From the macrosco pically not-visible/not-palpable MRI-detected abnormalities, 58% were (p)re active lesions and 21% contained active demyelinating lesions. In contrast, visible and/or palpable brain tissue samples mainly contained chronic inac tive lesions. We conclude that MRI-guided sampling of brain tissue increase s the yield of active multiple sclerosis lesions, including active demyelin ating and, (p)reactive lesions.