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PS02.04 - Relation between perivascular mononuclear infiltrates and plaque formation in the cortex and basal ganglia in progressive multiple sclerosis (MS).
Cortical plaque loads in primary progressive (PP) and secondary progressive MS (SP) appear equal whereas meningeal perivascular mononuclear/lymphocytic infiltration (PMI) may be more pronounced in SP. Basal ganglia may also be a predilection site in progressive MS.
To compare cortical and basal ganglia plaque formation and PMI in large tissue areas from clinically well-defined PP and SP patients.
Large brain sections from clinically well-described patients with PP (N=12), SP (N=14) and 11 age-matched controls were stained with HE, Luxol-fast blue and in patients additionally for proteolipid protein and CD68. T- and B-cells were confirmed in PMI’s by CD3 and CD 20 in 3 PP and 3 SP patients. We measured total plaque, microglia-rimmed slowly expanding plaque and macrophage-filled filled active plaque area loads (% of cortex or basal ganglia area), PMI densities (#/Cm2 or #/Cm meningeal length) and mean PMI size. PMI’s with min. size score one had 3-4 perivascular cell rows and 20-50 cells whereas max. score six had >19 rows and >500 cells. In one PP patient, cortical slowly expanding rims were confirmed by immunofluorescence showing IgG. Expanded Disability Status Scale (EDSS) score was estimated by chart review in a blinded fashion among 20 patients (10 PP and 12SP) from whom charts were available from two time points including one within three yrs. before death. Among these, we calculated ΔEDSS/yr. before death.
Tissue areas and meningeal lengths were similar in PP and SP. Both groups displayed similarly elevated cortical plaque loads and PMI densities in the cortex and meninges. However, meningeal PMI size as well as basal ganglia (6 SP vs 8 PP) plaque load and PMI density tended to be higher in SP vs PP. Meningeal PMI density correlated with total cortical plaque load while meningeal PMI size correlated with cortical slowly expanding plaque. Cortical PMI density and size correlated with active and slowly expanding (but not total) cortical plaque. PMI’s and plaque also correlated in the basal ganglia, albeit only in SP. Overall, age at death correlated negatively with PMI’s in the meninges, cortex and in the basal ganglia. Δ EDSS/yr. before death correlated with plaque load and tended to correlate with PMI’s, albeit only in the basal ganglia.
Perivascular immune activation in the meninges, cortex and basal ganglia may be pathogenic, driving grey matter demyelination in progressive MS.