Table 5.

Comparison of deep grey matter (DGM) inflammation, neurodegeneration and iron density in relation to the cortex and white matter

		MS NADGM	MS normal-appearing cortex	MS normal-appearing white matter
CD3-positive T cells	Median	1.7	1.7	2.2
	Min.−Max.	0–6.6	0–5.2	0–12.2
CD68-reactive macrophages and microglia/mm2	Median	150.8	145.8	264.8*
	Min.−Max.	63.1–310.8	66–217	85.1–505.2
IBA-1-reactive macrophages and microglia /mm	Median	222.4	267.4	390.6*
	Min.−Max.	35.6–697.9	45.1–817.7	111.1–796.9
iNOS-reactive macrophages and microglia/mm2	Median	76.7	17.4*	9.6*
	Min.−Max.	32.1–174.8	0–158	0–107.6
p22-Reactive macrophages and microglia/mm2	Median	347.4	383.7	418.8
	Min.−Max.	122.4–704.3	125–788.2	177.1–793.4
% Of p22-positive area	Median	1.2	1.4	1.7
	Min.−Max.	0–7.3	0.1–7.7	0.2–7
APP-reactive neuronal cell bodies/mm2	Median	0.3	0
	Min.−Max.	0–3.5	0–2.5
APP-reactive axonal spheroids/ mm2	Median	3	0	0*
	Min.−Max.	0–55.6	0–8.7	0–34.7
% E06-reactive neurons	Median	69.1	33.9*
	Min.−Max.	19.8–99.0	2.5–86.7
E06-reactive axonal spheroids/mm2	Median	1.5	0*	0*
	Min.−Max.	0–224	0–7.4	0–2.6
E06-reactive thin cellular processes/mm2	Median	5.4	0*	0*
	Min.–Max.	0–150.5	0–12.2	0–194.4
E06-reactive oligodendrocytes/mm2	Median	15.2	0*	0*
	Min.−Max.	0–72.1	0–34.7	0–128.5
E06-reactive lipofuscin/mm2	Median	29.2	17.4*	3.5*
	Min.−Max.	1.7–88.5	0–34.7	0–29.5
% E06-positive area	Median	3.5	0.1*	0.6*
	Min.−Max.	0.1–29.7	0–4.6	0–29
Oxidised DNA-reactive nuclei/mm2	Median	3.5	0*	0*
	Min.−Max.	0–19.7	0–15.6	0–12.2
Iron density	Median	654.5	306.3*	330.3*
	Min.−Max.	391.6–1031.2	238.9–377.7	222.3–733.9

This table depicts a comparison among the extent of inflammatory infiltrates, neurodegeneration and iron density in the normal-appearing deep grey matter (NADGM) (n=30) and the normal-appearing cortex (n=11) and white matter (n=24) of patients with MS. The values represent the median values and range.

*Significant p values after correction for multiple testing in comparison with NADGM.

Microglia and macrophage counts are pooled in order to facilitate the description. In patients with MS, normal-appearing white matter in the internal capsule expressed significantly more CD68 (p<0.001) and IBA-1 (p=0.027) compared with those in the NADGM. All evaluated E06-reactive structures, such as neurons (p<0.001), axonal spheroids (p=0.015 and p=0.002, respectively), thin cellular processes (p=0.014 and p=0.008, respectively), oligodendrocytes (p<0.001 and p<0.001, respectively) and lipofuscin (p=0.021 and p<0.001, respectively), were expressed at significantly higher levels in NADGM than in normal-appearing white matter or cortex. Similarly, the levels of oxidised DNA-reactive nuclei (p=0.039 and p<0.001, respectively) and the percentage of area data (p<0.001 and p=0.004, respectively) were greater in the NADGM than in normal-appearing white matter or cortex. APP-positive axonal spheroids were more often found in the NADGM than in the normal-appearing white matter (p=0.006). The iron content of NADGM was also significantly higher than that in cortical grey matter and normal-appearing white matter (p<0.001 and p<0.001, respectively).

APP, amyloid precursor protein; IBA-1, ionised calcium-binding adapter molecule 1; iNOS, inducible nitric oxide synthase; MS, multiple sclerosis.