Brain, Vol. 124, No. 8, 1635-1645,
August 2001
© 2001 Oxford University Press
Post-mortem MRI-guided sampling of multiple sclerosis brain lesions
Increased yield of active demyelinating and (p)reactive lesions
1 Department of Pathology, Division of Neuropathology, MS Centre for Research and Care (MSCRC), Departments of 2 Radiology and 3 Neurology, MS-MR Centre, Vrije Universiteit Medical Centre and 4 Netherlands Brain Bank, Amsterdam, The Netherlands
Correspondence to:
Dr Corline J. A. De Groot, Department of Pathology, Division of Neuropathology, MS Centre for Research and Care, Vrije Universiteit Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands E-mail: cja.degroot{at}vumc.nl
Macroscopic sampling of multiple sclerosis lesions in the brain tends to find chronic lesions. For a better understanding of the dynamics of the multiple sclerosis disease process, research into new and developing lesions is of great interest. As MRI in vivo effectively demonstrates lesions in multiple sclerosis patients, we have applied it to unfixed post-mortem brain slices to identify abnormalities, in order to obtain a higher yield of active lesions. The Netherlands Brain Bank organized the rapid autopsy of 29 multiple sclerosis patients. The brain was cut in 1 cm coronal slices. One or two slices were subjected to T1- and T2-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 in 10% formalin and paraffin-embedded, and the corresponding area in the adjacent half was snap-frozen in liquid nitrogen. In total, 136 out of 174 brain tissue samples could be matched with the abnormalities seen on T2-weighted MRIs. The stage of lesional development was determined (immuno) histochemically. 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 images represented active lesions, including lesions localized in the normal appearing white matter, without apparent loss of myelin but nevertheless showing 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 macro-scopically not-visible/not-palpable MRI-detected abnormalities, 58% were (p)reactive lesions and 21% contained active demyelinating lesions. In contrast, visible and/or palpable brain tissue samples mainly contained chronic inactive lesions. We conclude that MRI-guided sampling of brain tissue increases the yield of active multiple sclerosis lesions, including active demyelinating and (p)reactive lesions.
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