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Characterization of MS lesions

It is crucial that all MS tissue blocks are carefully characterized and the MS lesions, if present, are precisely characterized/staged 1–6 for white and grey matter lesions, including subscores for myeloid activity (see figure  and table below). We invested a lot of effort over the past 8 years to characterize all MS tissue that had been dissected since the start of the NBB in 1990 (>3,000 blocks containing >7,500 MS lesions). This work has been made possible by grants of the Vriendenloterij and the Stichting MS Research. We will continue this characterization for all current and upcoming MS autopsies. This implies that sections of the formalin part of the mirror blocks containing MS lesions and NAWM dissected by MRI guidance, as well as all diagnostic mirror blocks from the brain stem, hippocampus, basal ganglia and spinal cord, are double-stained for PLP/HLA and Kluver. Sections with the HLA/PLP double staining are photographed and the characterization is indicated in codes of these photographs (figure and table below). This facilitates the search of MS tissue to address all different research questions (see publications). The coming 4 years, NBB-MS will also perform bielschowsky silver staining (axons) as well as T cell (CD3), B cell (CD20) and plasma cell (CD138) stainings to further characterize the lesions for neuro-axonal damage and adaptive immune cell infiltration, respectively.

In addition to the characterization of all MS tissue blocks, the final diagnosis of the donor will be determined by our neuropathologist based on the diagnostic blocks and 5 representative MS lesions of the patient, together with the clinical information that is summarized and translated into English by one of the three clinical summarizers of the NBB. After explicit approval of the donor during life, the final diagnosis will be sent to the general practitioner of the relatives of the donor to inform the family on the disease status of their deceased relative.

Figure: Classification of MS lesion and myeloid activity (scores 0. 0.5, 1 represent myeloid sub-scores 1, 2 and 3 in the official characterization) in the MS lesions according to Luchetti et al., 2018 (see publications staff NBB).

 Code   Description
0 Normal-appearing white matter (NAWM: hardly any HLA reactivity, no demyelination)
1 Reactive (groups of HLA-positive microglial cells, no demyelination)
2 Active lesion (demyelination, HLA-positive microglial cells throughout the lesion). Sub score 1–3 reflects degree of activation of HLA positive microglial cells: ramified appearance = 1, up to big rounded foamy morphology = 3
3 Mixed active/inactive (chronic active) lesion (hypo- cellular, gliotic center, active border with HLA-positive macrophages/microglial cells). Sub score 1–3 reflects degree of activation of HLA-positive microglial cells: ramified appearance = 1, up to big rounded foamy morphology = 3
4 Gliotic inactive hypocellular lesion, with some HLA- positive microgliosis

Grey matter lesion (for cortex, not for spinal cord):

Type I = mixed grey-white matter lesion

Type II = grey matter lesion

Type III = subpial demyelination

Type IV = grey matter lesion that stops exactly at the border with white matter

6 Shadow plaque



Table: Staging of MS lesions according to Luchetti et al., 2018. Lesion scores (1–6) and myeloid activation sub- scores (1–3 see figure above) are indicated in photographs of HLA-PLP stained sections and used to select tissue for MS tissue applicants.

Characterization of MS lesions